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CHAPTER 16

Passive Monoclonal and Polyclonal

Antibody Therapies
J. PETER R. PELLETIER, MD, FCAP, FASCP •
FAISAL MUKHTAR, MBBS, MD, FCAP, FASCP

PASSIVE POLYCLONAL ANTIBODIES against human thymus lymphocytes in rabbits and

THERAPY horses, respectively. They are used in prevention and/
Passive Polyclonal Antibody Treatment or treatment of renal transplant rejection worldwide.1e7
Overview
Polyclonal immunoglobulins have been in use since the History of antibody use. rATG induction in combina-
19th century to protect against infectious agents, toxins, tion with immunosuppressive therapy is more effective
and disease conditions such as those with an autoim- in preventing episodes of acute renal graft rejection in
mune etiology. These immunoglobulin preparations adult renal transplant recipients, in recurrent episodes
of acute rejection,8,9 and those acute rejections that are
are made from pools of selected human donors or
animals with high titers of antibodies against viruses not responsive to high-dose corticosteroid therapy than
and toxins. These antibody treatments provide passive other monoclonal antibody preparations.10,11 rATG
transfer of high titer antibodies that either reduces risk recipients had a lower incidence of biopsy-confirmed
or reduces severity of infection. They are used to prevent acute rejection episodes,12 greater event-free survival up
hemolytic disease of the newborn and modify inflamma- to 10 years posttransplantation, and greater graft
tory reactions. Earlier drugs were very nonselective and survival up to 5 years posttransplantation.13
patients frequently succumbed to infection due to sup-
pression of both antibody-mediated (humoral) and Mechanisms of action. The exact mechanism of these
cell-mediated arms of the immune system. Today, the polyclonal antibodies has not been fully
principal approach is to alter lymphocyte function using understood.3,4,14e20 However, being polyclonal, they
drugs or antibodies against immune proteins. However, display specificity toward a wide variety of surface anti-
with the advent of human organ and tissue transplanta- gens (Ags) expressed on T and B-lymphocytes, dendritic
cells, natural killer (NK) cells, and endothelial cells.
tion (e.g., kidney, heart, bone marrow, and/or peripheral
blood stem cells) as treatment options, these polyclonal However, T-cell depletion is considered to play a key
antibody therapies in combination with other treatment role by modulating the expression of lymphocyte
regimens are being used to lower the ability of the body’s surface antigens involved in a wide variety of
immune system to reject these transplants. However, functions such as T-cell activation to endothelial
their use is not without risk, as complications include adherence, activation of certain transcription factors,
development of immune complexes and severe and interference with numerous immune cell
allergic reactions. A summary of these polyclonal anti- processes, such as cytokine production, chemotaxis,
body therapies may be found in Table 16.2. endocytosis, cell stimulation, and proliferation.14e20
In vitro studies indicate that binding of eATG to cells
is generally nonspecific; the drug binds to visceral tis-
Immunosuppressive Agents: Disease sues, including thymus and testis cell membranes and
Modifying nuclear and cytoplasmic components of tissues such
Antithymocyte globulin (rabbit)/thymoglobulin; as tonsil, kidney, and liver,21 and is extensively bound
antithymocyte globulin (equine)/Atgam to bone marrow cells,22 and to other peripheral blood
Description. Rabbit antithymocyte globulin (rATG) cells besides lymphocytes.21
and equine antithymocyte globulin (eATG) are puri-
fied, pasteurized preparation of lymphocyte depleting Diseases treated. As mentioned earlier, both antithy-
polyclonal gamma immunoglobulin (IgG) raised mocyte globulins are used for treatment and prevention

Immunologic Concepts in Transfusion Medicine. [Link]

Copyright © 2020 Elsevier Inc. All rights reserved. 251
252 Immunologic Concepts in Transfusion Medicine

of acute renal allograft rejection.2e8 More rATG recipi- TIG can only neutralize unbound exotoxin; it does
ents have been reported to achieve the endpoint of suc- not affect toxin already bound to nerve endings.31
cessful response (return of serum creatinine levels to
baseline by end of treatment or within 14 days of treat- Diseases treated. TIG is used to provide passive im-
ment initiation). However, among those who achieved munity to tetanus as part of a postexposure prophylaxis
a successful response, fewer episodes of recurrent rejec- regimen following an injury in patients whose immuni-
tion occurred with rATG within 90 days of treatment zation is incomplete or uncertain or if it has been more
cessation.2 eATG is also used for treating moderate-to- than 10 years since last dose of tetanus toxoid.1,3e9
severe aplastic anemia in patients who are unsuitable
for bone marrow transplantation.3,23,24 Adverse reaction. Slight soreness at injection site,
mild fever, and rarely sensitization to repeated injec-
Adverse effects. The most common adverse effects are tions of human immune globulin has been reported.28
fever, thrombocytopenia, leukopenia, gastrointestinal
disorders, and/or concurrent infection.1,2 Cytomegalo- Antitoxin and Immune Globulins: Disease
virus (CMV) infection was generally higher with rATG Modifying
except in high-risk patients.1,25 eATG therapy may Cytomegalovirus immune Globulin/Cytogam
result in reactivation of or infection with CMV, herpes Description. Cytomegalovirus immune globulin IV
simplex virus,25 or EpsteineBarr virus.26 The incidence (CMV-IG) is a purified immune globulin (hyperimmune
of malignancies is generally lower with rATG therapy.27 globulin) that contains immunoglobulin G (IgG)
This product is made of equine and human blood derived from pooled adult human plasma selected for
components, so it may carry a risk of transmitting high titers of anti-CMV antibodies.32
infectious agents such as viruses, and theoretically, the
CreutzfeldteJakob disease (CJD) agent. Mechanisms of action. CMV-IG provides relatively
high concentration of antibodies directed against
Update. There has been recent evidence that the addi- CMV. It provides prophylaxis against CMV infection
tion of human anti-T-lymphocyte globulin (ATLG) or disease in immunocompromised individuals.32e43
plus cyclosporine and methotrexate to standard graft- Results from in vitro studies and mice indicate that
versus-host disease (GVHD) prophylaxis is preferred anti-CMV antibodies can neutralize the pathogenic
over standard GVHD prophylaxis alone because it properties of CMV.42e44 As CMV usually targets a
improves the probability of survival without relapse population of bone marrow-derived myeloid lineage
and of chronic GVHD after myeloablative peripheral progenitor cells, antibody-neutralization of the virus
blood stem-cell transplantation from a human alone may not be enough to prevent or make active
leukocyte antigen (HLA)-identical sibling donor for disease less severe in already CMV-infected
patients with acute leukemia in remission. individuals.42,44e47
Additionally, this therapy provides better quality of life
and shorter immunosuppressive treatment compared Disease treated. CMV-IG provides passive immunity
to standard GVHD prophylaxis without ATLG.22 to individuals who are at risk for primary CMV
infection/disease, or secondary CMV disease
Antitoxin and Immune Globulins: Disease (reactivation of CMV).41,42,44e46,48e51 It is also
Modifying prescribed for the prophylaxis of CMV disease
Tetanus immune globulin/Baytet/Hypertet associated with transplantation of kidney, lung, liver,
Description. Tetanus immune globulin (TIG) is a spe- pancreas, and heart. With the exception of CMV-
cific solvent-detergent-treated plasma-derived product seronegative recipients of kidneys from CMV-
obtained from donors immunized with tetanus seropositive donors, CMV-IG prophylaxis should be
toxoid. TIG contains tetanus antitoxin that provides considered in conjunction with ganciclovir.
temporary passive immunity to individuals who have
low or no immunity to the toxin produced by Adverse reactions. Most frequent adverse reactions re-
Clostridium tetani.28,29 ported are flushing, chills, muscle cramps, back pain, fe-
ver, nausea, vomiting, arthralgia, and wheezing.32,34e36
Mechanisms of action. TIG contains tetanus anti- There is a slight risk of hemolysis, as intravenous immu-
toxin antibodies, which neutralize the free form of the noglobulin (IVIG) products can contain blood group an-
powerful exotoxin produced by Clostridium tetani.28,30 tibodies, which may act as a hemolysin and induce
 CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies 253

in vivo coating of red blood cells with immunoglobulin, Most common adverse reactions to crofab are urticaria,
causing a positive direct antiglobulin reaction. rash, nausea, pruritus, and back pain.61,62
Transfusion-related acute lung injury (noncardiogenic
pulmonary edema) and thrombotic events have been High antibody titer influenza fresh frozen
reported in patients receiving IVIG preparations.32 plasma
Similar to all other products made from human Description. Use of convalescent (persons who have
plasma, this CMV-IG also carries the possibility for recovered from a particular infection) donor plasma
transmission of blood-borne viral agents and the CJD with high hemagglutination inhibition titer against
agent. However, this IVIG is treated with a solvent deter- certain influenza strains has been recommended as a
gent viral inactivation procedure to inactivate a wide primary therapy for severe respiratory infectious dis-
spectrum of lipid-enveloped viruses, including HIV-1, eases including influenza, severe acute respiratory syn-
HIV-2, Hepatitis B, and Hepatitis C. drome, and Middle East respiratory syndrome.63

Antivenin [latrodectus mactans]/black History of antibody use. A meta-analysis of previous

widow spider antivenindantivenin Micrurus cohort studies during the 1918 influenza pandemic
fulvius/eastern and Texas coral snake showed a case-fatality rate of 16% among subjects
antivenindcrotalidae polyvalent immune treated with plasma, serum, or whole blood compared
Fab/Crofab to 37% among controls. Similarly, in 2009, a cohort
Description. These antivenins are sterile, nonpyro- study using convalescent plasma for the treatment of
genic, purified, and lyophilized preparation of specific pandemic H1N1 influenza resulted in a mortality of
venom-neutralizing serum globulins obtained from 20% in the treatment group versus 54% in the control
the blood serum of healthy horses exposed to the group.64
venom of black widow spiders and eastern coral snake
(Micrurus fulvius) venom, respectively.52e55 In contrast, Mechanisms of action. Antiinfluenza convalescent
crofab is an antivenin made up of ovine Fab plasma decreases the rate of viral shedding measured
(monovalent) immunoglobulin fragments obtained by neutralizing antibody titer and hemagglutination in-
from blood of healthy sheep immunized with North hibition.65 Both preexisting immunity (previous infec-
American Crotalinae subfamily of venomous snakes tions and vaccinations) as well as any immune
that includes rattlesnakes, copperheads, cottonmouth, response occurring after illness onset makes this mech-
or water moccasins.56 anism of action more complex.
Mechanisms of action. Mode of action of these anti-
venins is unknown.52 However, they probably act by Disease classifications treated. Influenza, severe
neutralizing venom of black widow spiders and coral acute respiratory syndrome, and Middle East respiratory
snakes.54 Crofab is a venom-specific Fab fragment of syndrome.63
IgG that works by binding and neutralizing venom
toxins, facilitating their redistribution away from Adverse effects. Convalescent plasma seems safe.
target tissues and their elimination from the body.56 The serious adverse events reported are related to the
underlying influenza, its complications, preexisting
Disease treated. These antivenins are indicated for comorbidities, and not due to the convalescent plasma
patients with symptoms due to bites by black widow usage.
spider (Latrodectus mactans)52 and bites of two genera
of coral snakes, that is, Micrurus (including the eastern High antibody titer ebola fresh frozen plasma
and Texas varieties) and Micruroides (the Sonoran or Description. Antibodies to the Ebola virus (EV) in
Arizona variety), found in southeastern Arizona and whole blood or plasma from convalescent donors
southwestern New Mexico.52,57e59 Antivenin Micrurus may be effective in the treatment of EV infection.
fulvius (equine origin) is indicated only for treatment
and management of adult and pediatric patients
exposed to North American crotalid envenomation.54 History of antibody use. The World Health Organiza-
tion (WHO) has stated that convalescent blood or
Adverse effects. Immediate systemic reactions plasma is an option in the treatment of Ebola.66 In
(allergic reactions or anaphylaxis) and death can occur 1999, transfusion of locally collected convalescent
in patients sensitive to antivenin from horse serum.52,60 blood helped to decrease Ebola mortality.67 Therefore,
254 Immunologic Concepts in Transfusion Medicine

WHO has recommended the collection of convalescent history of hypersensitivity to papaya or papain unless
plasma to treat patients with Ebola virus infection. the benefits outweigh the risks.

Mechanisms of action. This fresh frozen plasma Immune Globulins: Antiinfectious

(FFP) has high titers of antibodies directed against Hepatitis B immune globulin/HepaGam B/nabi-
Ebola virus.68 HB/BayHepB/HyperHEP B S/D
Description. Hepatitis B immune globulin (HBIG) is a
Adverse effects. Convalescent plasma seems safe specific immune globulin (hyperimmune globulin)
with few adverse effects.69,70 that contains antibody to hepatitis B surface antigen
(anti-HBs) prepared from plasma of healthy donors
Digoxin immune Fab/DigiFab; Digibind with high titer (>1:100,000) of anti-HBs antibody. It
Description. Digoxin immune Fab is a sterile, purified, provides temporary passive immunity against
lyophilized monovalent preparation of bovine immu- hepatitis B virus (HBV).98e104
noglobulin Fab fragments that binds to digoxin. These HepaGam-B is a solvent/detergent-treated sterile so-
Fab fragments are obtained from the blood of healthy lution of purified gamma globulin containing antibody
sheep immunized with a digoxin derivative, digoxindi- to HBs antigen that contains high titers of anti-HBs
carboxymethoxylamine, a digoxin analogue that con- from plasma donated by healthy screened donors.
tains the functionally essential Both HBIG and HepaGam-B are manufactured by a sol-
cyclopentaperhydrophenanthrene: lactone ring moiety vent/detergent (S/D) treatment procedure that is effec-
coupled to keyhole limpet hemocyanin. The final prod- tive in inactivating lipid-enveloped viruses such as
uct is prepared by taking the immunoglobulin fraction hepatitis B virus, hepatitis C virus, and human immu-
of the ovine serum, digesting it with papain, and nodeficiency virus type 1 and type 2. However, S/D is
isolating the digoxin-specific Fab fragments by affinity less effective against nonlipid-enveloped viruses such
chromatography.71e79 as hepatitis A virus and parvovirus B-19.100,101,104

Mechanisms of action. DigiFab or Digibind have Mechanisms of action. It provides passive immuni-
antigen-binding fragments that bind to free digoxin zation for individuals exposed to the hepatitis B virus
molecules that results in an equilibrium shift away by binding to the surface antigen and reducing rate of
from binding to receptors, thereby reversing the hepatitis B infection.
cardiotoxic effects of the glycoside.71,72,75,76,78,80e87
Subsequently, Fab-digoxin complexes are cleared by Diseases treated. HBIG provides passive prophylac-
the kidney and reticuloendothelial system. Due to tic immunity to HBV infection for prevention of peri-
papain treatment, the Fab fragments lack the antigenic natal HBV infection in neonates born to HBs antigen-
determinants of the Fc fragment resulting in reduced positive (HBsAg-positive) mothers,100e106 for
immunogenicity to patients as opposed to intact postexposure prophylaxis in susceptible individuals
immunoglobulin products.71,72,75,76,78,79,84,88,89 exposed to HBV or HBsAg-positive materials (e.g.,
blood, plasma, serum),100e104,107e109 sexual exposure
Diseases treated. Digoxin immune Fab is indicated to HBsAg-positive persons, for household exposure to
for patients with either life-threatening or potentially persons with acute HBV infection, and for prevention
life-threatening digoxin toxicity or overdose.71,79,90e95 of HBV recurrence in liver transplant recipients who
Data from clinical trials have showed that both are HBsAg-positive (HepaGam-B only).104,110e117
DigiFab and Digibind reduce levels of free digoxin in HBIG is not indicated for treatment of active hepatitis
the serum to below the limit of assay quantitation for B infection and is ineffective in the treatment of
several hours after Fab administration. chronic active hepatitis B infection.105

Adverse reactions. Digoxin immune Fab (ovine) Adverse reactions. The local adverse reactions that
generally is well tolerated following intravenous (IV) may occur at the site of injection after intramuscular
administration.71e73,76,78 Hypokalemia may occur, (IM) administration are pain, tenderness, swelling,
sometimes developing rapidly in patients receiving and erythema.100,101,109 The systemic effects that may
digoxin immune Fab (ovine).71,72,79,96,97 DigiFab occur after IM administration are urticaria, angioedema,
should not be administered to patients with a known nausea, vomiting, myalgia, headache, flu- or cold-like
 CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies 255

symptoms, lightheadedness, and malaise have been and nausea. Severe hypersensitivity reactions may occur
reported.100,101,104 following administration of VZIG.118

Varicella zoster immune globulin/VariZIG Rimabotulinumtoxin B/Myobloc

Summary. Varicella zoster immune globulin (VZIG) is Summary. Rimabotulinumtoxin B, a type B botuli-
a specific immune globulin (hyperimmune globulin). num toxin produced by fermentation of the bacterium
VZIG is prepared from plasma of donors selected for Clostridium botulinum type B (Bean strain), is a neuro-
high titers of antibodies to varicella zoster virus (anti- muscular blocking agent (neurotoxin) and inhibitor
VZV) and used to provide temporary passive of acetylcholine release at motor nerve
immunity against VZV.118e120 terminals.123e126

Mechanisms of action. VZIG acts by neutralizing Mechanisms of action. Rimabotulinumtoxin B and

varicella zoster virus via high titers of IgG antibodies other botulinum toxin serotypes act by inhibiting
present in the plasma used. acetylcholine release at the neuromuscular junction
via a three-step process, that is, toxin binding, toxin
Diseases treated. VZIG is used for postexposure pro- internalization, and inhibition of acetylcholine release
phylaxis of varicella (chickenpox) in individuals who into the neuromuscular junction leading to chemical
do not have evidence of varicella immunity and are at denervation and flaccid paralysis.123,124,126,127
high risk for severe varicella infection and its complica-
tions. These high risk individuals include immunocom- Diseases treated. Rimabotulinumtoxin B is used for
promised patients such as neonates whose mothers management of adults with cervical dystonia
have signs and symptoms of varicella around the time (also called as spasmodic torticollis) to reduce severity
of delivery (i.e., 5 days before to 2 days after), premature of abnormal head positioning and neck pain through
infants born at
28 weeks of gestation who are exposed reduction of undesired or excessive contraction of
during the neonatal period and whose mothers do not striated or smooth (involuntary) muscle.128e131
have evidence of immunity, premature infants born
at <28 weeks of gestation or who weigh 1000 g at birth Adverse reactions. The most common adverse effects
and were exposed during the neonatal period regardless reported with Botulinum toxin are dry mouth,
of their mothers’ evidence of immunity status, and dysphagia, dyspepsia, and injection site pain.123,132e134
finally pregnant women.118,119,121,122 Serious hypersensitivity reactions have been rarely re-
VZIG is now recommended for outbreak control and ported with onabotulinumtoxin A.127
postexposure treatment, and the vaccine is available to
children with humoral immunodeficiencies and selected Botulism immune globulin/BabyBIG
children with HIV infection.122 Use of VZIG for postex- Summary. Botulism immune globulin IV (BIG-IV) is a
posure prophylaxis in pregnant women exposed to specific immune globulin (hyperimmune globulin) that
VZV may prevent or reduce severity of varicella in the is prepared from plasma of adult volunteer donors
woman but does not prevent fetal infection.119,121 immunized with pentavalent botulinum toxoid, which
VZIG is not indicated for individuals who previously neutralizes free botulinum toxin types A and B. It is
received age-appropriate varicella vaccination and sub- one of the most poisonous substances known and
sequently became immunocompromised because of exists in seven antigenic variants (types A to G).120,121,135
disease or immunosuppressive therapy later in life.
Bone marrow transplant recipients should be consid- Mechanisms of action. BIG-IV is a human-derived
ered susceptible to varicella regardless of previous his- antitoxin that neutralizes botulinum toxin. BIG-IV has
tory of varicella or varicella vaccination in themselves a half-life of approximately 28 days in vivo and large
or their donors. However, those who develop varicella capacity to neutralize the toxin.135
or herpes zoster after transplantation should be consid-
ered immune to varicella.119 Disease treated. Infant botulism occurs when young
infants ingest spores of Clostridium botulinum that then
Adverse reactions. The most common adverse effects germinate, colonize the GI tract, and produce botuli-
reported with VZIG in clinical trials in pregnant women, num toxin. This neurotoxin causes generalized weak-
infants, and immunocompromised adults and children ness and loss of muscle tone. A single infusion will
were injection site pain, headache, chills, fatigue, rash, neutralize the toxin for at least 6 months and toxins
256 Immunologic Concepts in Transfusion Medicine

type A or B that may be absorbed from the colon of an Mechanisms of action. The exact mechanism of
infant younger than 1 year old.121,135e139 action of Rho(D) immune globulin in the
suppression of formation of anti-Rho(D) is not fully
Adverse effect. Mild, transient, blush-like erythe- known.
matous rash on the face or trunk occurred in 9% In the treatment of preventing D alloimmunization,
e14% of infants receiving BIG-IV in clinical RhIG binds to Rho(D) antigen that entered the
studies.135,140 maternal circulation during fetalematernal hemor-
rhage (FMH) involving an Rho(D)-positive fetus or
Rabies immune globulin/bayrab/HyperRAB, transfusion with Rho(D)-positive blood, preventing
imogam Rabies, KedRAB stimulation of the mother’s primary immune response
Description. Rabies immune globulin (RIG) is a ster- to Rho(D) antigen. Therefore, by preventing the active
ile solution of specific IgG that contains antibody to production of anti-Rho (D) by the mother, the risk of
rabies antigen. It is used to provide temporary passive hemolytic disease of the fetus and newborn in future
immunity to rabies infection as part of a postexposure pregnancies is decreased.145e149
prophylaxis regimen in unvaccinated individuals In the treatment of idiopathic thrombocytopenic
exposed to the disease or virus.141e144 purpura (ITP), administration of Rho(D) immune glob-
ulin to Rho(D)-positive individuals is believed to cause
Mechanisms of action. RIG is a human-derived transient mononuclear macrophage Fc receptor (FcR)
antitoxin that neutralizes rabies virus so that virus blockade by complexes within the reticuloendothelial
spread is reduced and its infective or pathogenic system, particularly the spleen, which spares the pa-
properties are inhibited. Specific rabies antibodies tient’s IgG-coated platelets. This FcR blockade
present in RIG neutralizes rabies. It should be used in and decreased Fc-mediated phagocytosis of antibody-
conjunction with rabies vaccine and can be coated platelets result in increases of platelet counts in
administered through the seventh day after the first ITP patients.145,149,151e156
dose of vaccine is given. RIG provides immediate,
temporary rabies virus-neutralizing antibodies until Diseases treated. Prevent D alloimmunization in D-
the patient responds to active immunization and negative women of childbearing potential if the
produces virus-neutralizing antibodies.121,141e144 neonate is Dþ, weak-D positive, or D untested, and
following perinatal events associated with FMH such
Diseases treated. Given to all persons suspected of as abortion, ectopic pregnancy, amniocentesis,
exposure to rabies with one exception, those who chorionic villus sampling, external cephalic version,
have been previously immunized with rabies vaccine abdominal trauma, and antepartum hemorrhage. It is
and have a confirmed adequate rabies antibody titer also used to prevent D alloimmunization in D-
should receive only vaccine. negative individuals who receive Dþ blood
components such as whole blood-derived platelets,
Adverse reactions. Most common local adverse ef- apheresis platelets, and/or granulocytes. Similarly, it is
fects include tenderness, pain, muscle soreness, or used for the treatment of ITP in Dþ patients who had
stiffness that may occur at the site of injection. Low- not undergone splenectomy.145e147,149,151e153,157e164
grade fever, headache, and malaise may also Some preparations of Rho(D) immune globulin may
occur.141e143 be administered IM or IV (Rhophylac, WinRho SDF),
whereas others are labeled for IM use only
Immune Globulins: Immunomodulation (MICRhoGAM, RhoGAM, HyperRHO S/D Full Dose,
Rho(D) immune globulin/WinRho; RhoGam; HyperRHO S/D Mini-Dose).145e147,149,165 When
Rhophylac, MicRhoGAM, BatRhoD, HyperRho used for ITP treatment, RhIG must be administered
Summary. Rho(D) immune globulin (RhIG) consists IV.145,149
of anti-Rho(D) IgG antibodies to the red blood cell
Rho(D) antigen. RhIG is prepared from human pools Adverse reactions. Generally, mild with the most
of plasma of Rho(D)-negative donors immunized common being headache, fever, chills, pain at the injec-
with Rho(D)-positive red blood cells after cold tion site and, rarely, hypersensitivity reactions. Some
alcohol fractionation, and subsequent purification and degree of hemolysis is inevitable, but this is predictable
infectious disease reduction technologies.145e150 and transient.146,147
 CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies 257

Immunoglobulin (generic)/bbrands: Bivigam, production, suppression of inflammatory cytokines and

Carimune, Cuvitru, Flebogamma, Gammagard, chemokines, and/or antiidiotypic regulation of
GamaSTAN, Gammaked, Gammaplex, autoreactive B-lymphocytes or antibodies.
Gamunex-C, Hizentra, Hyqvia, Octagam As IVIG contains a diverse group of antibody speci-
Privigen ficities, which protects recipients against multiple infec-
Summary. Immune globulin IM (IMIG), immune tions by eliminating opsonized infectious organisms via
globulin IV (IVIG), and immune globulin subcutane- antibody-dependent cell-mediated cytotoxicity or by
ous are sterile, nonpyrogenic preparations of globulins complement activation. This is followed by lysis and/
containing many antibodies normally present in adult or neutralization of soluble infectious proteins by im-
human blood. Immune globulins (IG) are collected mune complex formation and elimination through
either by whole blood donations as recovered plasma the RES.166,170,173e175
(20%), or by apheresis as source plasma (80%). IVIG
is a highly purified product consisting mostly of IgG Diseases treated. IVIG is indicated for the treatment
with a half-life of 21e28 days. of primary immune deficiency, secondary immune defi-
Hyperimmune globulin (Hyper-Ig) products are ciency, ITP, Kawasaki disease, and congenital hypogam-
manufactured from donors with high Ig titers with spec- maglobulinemia. Currently, there is an extensive list of
ificity to antigenic determinant(s) of interest. High titers diseases for which IVIG could be used. It also has
of these donors can be achieved by natural immunity, immunomodulatory properties resulting in an
prophylactic immunizations, or through targeted im- increasing list of both FDA-approved and
munizations. Hyper-Ig products should contain at least nonapproved indications.
fivefold-increased titers compared to standard prepara- IMIG is used to provide passive immunity to hepati-
tions of IVIG. tis A virus infection for preexposure or postexposure
IVIG production is regulated by the IUIS/WHO (In- prophylaxis in susceptible individuals who are at risk
ternational Union of Immunological Societies/World of or have been exposed to the virus. IMIG and IVIG
Health Organization), which require the following: are used to prevent or modify symptoms of measles
• Source material must be plasma obtained from a (rubeola) in susceptible individuals exposed to the
minimum pool of 10,000 donors; disease <6 days. IVIG is used for replacement therapy
• Product must be free of prekallikrein activator, ki- to promote passive immunity in patients with primary
nins, plasmin, preservatives, or other potentially humoral immunodeficiency who are unable to produce
harmful contaminants; sufficient amounts of IgG antibodies and in the man-
• IgA content and IgG aggregate levels need to be as agement of ITP to increase platelet counts, to prevent
low as possible; and/or control bleeding, or to allow these patients to
• Product must contain at least 90% intact IgG; undergo surgery.
• IgG should maintain opsonin activity, complement IVIG is used for prevention of bacterial infections in
binding, and other biological activities; patients with hypogammaglobulinemia and/or recur-
• IgG subclasses should be present in similar pro- rent bacterial infections associated with B-cell Chronic
portions to those in normal pooled plasma; Lymphocytic Leukemia. IVIG is used in conjunction
• Antibody levels against at least two species of bac- with aspirin therapy for initial treatment of the acute
teria (or toxins) and two viruses should be phase of Kawasaki disease. IVIG is also used to treat
determined; chronic inflammatory demyelinating polyneuropathy
• Product must demonstrate at least 0.1 international to improve neuromuscular disability and impairment,
units of hepatitis B antibody per mL, and hepatitis A and for maintenance therapy to prevent relapse.
radioimmunoassay titer of at least 1:1000; Furthermore, IVIG is used for maintenance treatment
• Manufacturer should specify the contents of the final to improve muscle strength and disability in adults
product, including the diluent and other additives, with multifocal motor neuropathy.166e201
and any chemical modification of IgG.166e172
Adverse reactions. Approximately 2%e10% of infu-
Mechanisms of action. The mechanisms of Ig-induced sions are associated with adverse reactions that include
immunomodulation are incompletely understood but those at the infusion site (erythema, pain, swelling, pru-
include macrophage Fc receptor blockage by immune ritus, heat), phlebitis, eczema, fever, chills, myalgias,
complexes formed between IVIG and native antibodies, malaise, flushing, rash, diaphoresis, pruritus, broncho-
modulation of complement, suppression of antibody spasm, chest pain, back pain, extremity pain, dizziness,
258 Immunologic Concepts in Transfusion Medicine

blood pressure changes, nausea, vomiting, and associated with immunogenicity that can cause a
headache.167,170,172,177e179,181e183 decrease in their effectiveness. Antineoplastic anti-
bodies can be associated with tumor lysis syndrome.
PASSIVE MONOCLONAL ANTIBODY Similarly, reactivation of underlying infections can
TREATMENT occur leading to progressive multifocal leukoencephal-
In the late 20th century (w1986), monoclonal anti- opathy, HBV, fungal, parasitic, or tuberculosis infec-
bodies were developed. The first monoclonal anti- tions. Other adverse reactions include but are not
bodies (Mabs) were of xenographic source and were limited to initiation of autoimmune disorders,
wrought with problems of immunogenicity. These increased risk for malignancy, cardiac arrhythmia,
early Mabs did not gain favor until chimerization angina/ischemia, cytopenias, hemorrhage, and allergic
took pace in the mid-1990s, and in 1998 two Mabs reactions including anaphylaxis, embryoefetal toxicity
were approved to treat one respiratory syncytial virus (if can cross placental barrier), and even death.
and the other certain breast cancers. Further develop-
ment to humanize and then generate fully human
Mab led to an evolution of therapies utilizing these TYPES OF ILLNESS TREATED
agents. Mabs are being researched or approved to treat Oncology
a multitude of diseases that include oncologic, inflam- Malignancies can be caused by infectious agents, toxins,
matory, autoimmune, cardiovascular, respiratory, or genetic mutations with changes in control of growth,
neurologic, allergic, benign hematologic, infectious, proliferation, or programmed cell death. Historically
orthopedic, coagulopathic, and metabolic indications these have been treated with a variety of radiation ther-
and to decrease disease morbidity (diminution of apies to eradicate malignant cells or with chemothera-
pain), modify disease progression (i.e., macular degen- peutic agents to enhance maturity, decrease
eration, diabetes), and potentially alter anatomic proliferation, or cause destruction of cancer cells. In
development. In this section of the chapter, we will re- some cases intense high-dose chemotherapy is used to
view the history of use of these passive monospecific cause cancer remission with stem cell transplants for
antibody therapies, their mechanism of action, subsequent rescue. Passive antibody therapy may
pharmacologic-therapeutic classification, particular replace or be additive to other pharmacology therapies
medical indication, adverse reactions, and potential and increase chances for complete remission, prolong
future use of these medications.201 disease-free survival, and overall survival.

Mechanism of action
Depending on the antigenic target of these antibodies B-cell chronic lymphocytic leukemia
multiple events are set into action. Immunologic Rituximab (Rituxan) is a chimeric murine/human Mab
changes occur as the specific antigens are presented (IgG1k) that binds to CD20 (human B-lymphocyte-
more efficiently to effector cells. Some of these actions restricted differentiation antigen, Bp35 {controlling dif-
create decreased inflammatory and allergic responses, ferentiation and possible calcium ion channel}). Its
while other effects generate antibody-dependent cyto- mechanism of action is not entirely clear and may
toxicity (ADCC) and complement-dependent cytotox- involve CDC and ADCC. Many studies have shown
icity (CDC). Other actions can block receptor this antibody to have an additive benefit to standard
interaction with ligands by either binding with ligands chemotherapy alone. This antibody has been approved
or their cognate receptors (i.e., allow activation of NK by the FDA to treat chronic lymphocytic leukemia (CLL)
cells). Interactions may also directly cause initiation of since 1997. Nowadays, this medication is often com-
programmed cell death (apoptosis), cessation of bined with ibritumomab in treating CLL (to be dis-
growth/replication/proliferation, or lead to changes in cussed with non-Hodgkin’s lymphoma).202,203
metabolism. Moreover, there are also antibodies against Alemtuzumab (Campath) binds to CD52 and is a
infectious agents to prevent cell adhesion for entry, humanized rat Mab (IgG1k) binding to receptors on
spread, replication, and contagion. Antibodies may both T and B cells as well as macrophages, NK cells,
also be directed against toxins leading to various and neutrophils, leading to CDC and ADCC. The resul-
methods of inactivation.201 tant cytopenias lead to a severe immunocompromised
state. Alemtuzumab was FDA approved as a single agent
Adverse reactions in the treatment of B-cell CLL in 2001.204
Depending on their mode of action, Mabs are associ- Ofatumumab (Ocrevus) is a human Mab (IgG1k)
ated with a myriad of side effects. They can be with CDC that binds to CD20 near the cellular
 CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies 259

membrane. In phase II studies, this agent had 86% AML cells, while in animal studies it has demonstrated
objective response rate (ORR) when used alone and significant decrease in tumor burden.217
with CHOP therapy had 100% ORR and 62% complete IMGN632 is an anti-CD123 antibody complexed to
remission (CR); whereas, in phase III trials, this Mab a DNA mono-alkylating agent. In vitro studies showed
showed ORR of 10% after rituximab relapse. This medi- it had more potency against AML cells than to normal
cation was approved by the FDA to treat CLL in myeloid progenitor cells. In animal models there was
2009.205 an excellent response rate against tumor cells. Ongoing
Monalizumab is a humanized Mab (IgG4k) that clinical trials will be completed in 2021.216
binds to CD94/NKG2A (an inhibitory signal receptor Talacotuzumab is a humanized monoclonal anti-
transmitter) on NK cells. Monalizumab demonstrated body (IgG1-2k) with specificity to interleukin (IL)-3 re-
blockade of NKG2A/HLA-E and restores the ability of ceptor subunit-a (CD123, a growth and differentiating
NK cells to lyse B cells in vitro. In addition, this Mab receptor). This antibody induces ADCC both in vitro
was shown to be of benefit in murine models. Ongoing and in animal models. Phase III clinical trials were
phase I/II studies will be completed in 2019.206 reportedly completed in 2018; published results are
Otlertuzumab is a humanized Mab fragment (IgG forthcoming.218
Fab’) with specificity to CD37 that induces both Samalizumab is a humanized Mab (IgG2/IgG4k)
ADCC and caspase-independent apoptosis. In a phase with specificity to CD200 (OX-2membrane glycopro-
II study both better progression-free survival (PFS) tein) is in phase II trials to be completed in 2021.219
and ORR were observed when used with bendamustine Ficlatuzumab is a humanized Mab (IgG1k) in a
compared to bendamustine used alone.207 phase I trial to treat refractory/relapsing AML to be
Urelumab is a human Mab (IgG4k) with specificity completed in 2020.220
to CD134 (an immune checkpoint inhibitor). This anti- Other Mab not demonstrating benefit in clinical tri-
body has completed safety phase I dosing trials. Higher als or withdrawn following postmarketing for AML
doses lead to significant hepatotoxicity. Safe dosing is include gemtuzumab ozogamicin (FDA approved
now established in clinical phase II studies to be 2000 withdrawn 2010 secondary to venoocclusive dis-
completed in 2020.208,209 ease) and lintuzumab (no added benefit over standard
Ulocuplumab is a human Mab with specificity to chemotherapy).221e223
CD184 (CXCR4). In vitro studies showed apoptotic ef-
fects via production of oxygen species that was not asso- Multiple Myeloma
ciated with better caspase activation than AMD3100. Daratumumab (Darzalex) is a human Mab (IgG1k)
Phase I studies were completed in 2014, no manuscripts with specificity to CD38 (functions reportedly include
were found for review. This medication is presently in receptor-mediated adhesion and signaling events, as
phase II trials against acute myelocytic leukemia well as important bifunctional ectoenzymatic activities
(AML) to be completed in 2021.210,211 that contribute to intracellular calcium mobilization.
Other monoclonal antibodies not demonstrating This Mab mechanism of action is thought to induce
benefit in clinical trials for CLL include apolizumab, dace- CDC, ADCC, antibody-dependent cellular phagocy-
tuzumab, and gomiliximab (aka lumiliximab)212e215 tosis, and apoptosis. This medication is used to treat re-
fractory and recurrent multiple myeloma.224,225
Silutuximab (Sylvant) is a chimeric Mab (IgG1k) with
Acute myelocytic leukemia specificity to IL-6. This medication was FDA approved in
AML is the leading cause of leukemic mortality in the 2014 for multicentric Castleman’s disease (MCD) with
United States (US). Over the last 10 years therapy has HIV negative and HHV-8 negative. There are ongoing
not changed significantly for this disease. Novel thera- studies in phase II clinical trials to be completed in
pies have been developed in the last decade, some 2019.226,227
showing temporal success and some showing a brighter
tomorrow.216 B-cell acute lymphoblastic leukemia (B-cell ALL)
AMG330 is a bispecific T-cell engager (BiTE) anti- Blinatumomab (Blincyto) is a mouse double heavy-
body with specificity for CD3 and CD33. This Mab is chain fragment (Murine {scFv - kappa e heavy} e
currently in clinical trials to be completed in 2020 for {scFv - heavy e kappa}) with specificity for CD19
treatment of AML. A BiTE antibody stimulates ADCC and CD3 known as a BiTE. This Mab’s mode of action
(via T cells) in the presence of antigenic targets on cells is by directing CD3þ effector memory T cells to
of interest. In vitro studies have shown effective lysis of CD19þ target cells leading to T-cell activation and B-
260 Immunologic Concepts in Transfusion Medicine

cell apoptosis. This biologic is used to treat relapsed/re- FcgR binding decreases ADCC of the T cells enabling
fractory cell ALL. In phase III trials event-free survival more tumor-specific T cell to remain active. This medi-
almost tripled and duration of remission almost cation was approved by the FDA in 2019 to treat triple
doubled.228e230 negative (estrogen receptor, progesterone receptor, hu-
man epidermal growth factor receptor-2) unresectable
Hodgkin’s lymphoma or metastatic breast cancers.237,238
Hodgkin’s lymphoma is a rare malignancy affecting
young adults with a peak incidence in patients Colorectal Cancer
>55 years old. Up to 40% of these patients can develop Bevacizumab (Avastin) is a humanized Mab (IgG1k)
relapsing disease. Brentuximab vedotin (Adcentrix) is a with specificity to vascular endothelial growth factor-a
chimeric humanized Mab drug conjugate (VEGF-A) that acts as an inhibitor of angiogenesis. It
(Mab þ linker þ payload {IgG1k þprotease cleavage was FDA approved for treatment of colorectal cancer
linker þ monomethyl auristatin E [MMAE]}) with spec- and has recently been approved for multiple other can-
ificity to CD30 (a cell membrane protein of the tumor cers including ovarian, fallopian cancers, renal cell car-
necrosis factor receptor superfamily member 8. MMAE cinoma, and recurrent glioblastoma multiforme
is a microtubule-disrupting agent. The combination of (GBM).239,240
this a Mab and drug conjugate disrupts the intracellular
microtubule network causing cell cycle arrest at G2/M Urothelial Carcinoma
stage and apoptosis. This medication has a 43% PFS Atezolizumab (Tecentriq) is FDA approved as a single
at 30 months.231 agent in urothelial carcinoma and for patients with dis-
Mab to look out for in the future include Camidan- ease progression despite other chemotherapy
lumab tesirine (ADCT-301) a human Mab (IgG1k). treatment.241,242
This Mab has specificity to CD25 (a IL-2 receptor alpha
subunit) with a drug conjugate. The drug is released Nonsmall cell lung cancer
intracellularly and causes DNA interstrand crosslinks. Atezolizumab (Tecentriq) is FDA approved as a single
This Mab is in phase I studies to be completed in agent for nonsmall cell lung cancer (NSCLC).
2019 for Hodgkin’s and non-Hodgkin’s T- and B-cell Bevacizumab (Avastin) is FDA approved for treat-
lymphomas. In addition, there are clinical phase I ment of locally advanced, recurrent or metastatic, non-
studies against multiple solid tumors to be completed squamous NSCLC.
in 2021.232,233 Nivolumab (Opdivo) is an FDA-approved human
Agents abandoned or not found to be beneficial Mab (IgG4k) immunoglobulin and blocks PD-1 pre-
include apolizumab, denintuzumab mafodotin (HBU- venting interaction PD-1 and its ligands PD-L1 and
12), iratumumab (MDX060), and lucatumumab PD-L2. It is used to treat RCC, NSCLC, Hodgkin’s lym-
(HCD122).212,234,235 phoma, melanoma, small cell lung cancer, colorectal
cancer, and squamous cell carcinoma of the head and
Anaplastic large cell lymphoma neck. In phase III clinical trials, nivolumab performed
Brentuximab vedotin (Adcentrix) is an FDA-approved better than docetaxel in the treatment of NSCLC.243e245
medication for patients with refractory or relapsed
anaplastic large cell lymphoma who achieved CR. This Ovarian/cervical fallopian cancer
Mab had 79% OS and 57% PFS at 5 years, with median Bevacizumab (Avastin) is FDA approved for treatment
response duration not reached at time of of locally advanced, recurrent or metastatic, ovarian,
publication.236 cervical, and fallopian cancers after treatment with
chemotherapy regimens and surgery.246
Breast Cancer
Atezolizumab (Tecentriq) is an FcgR bindingedeficient, Merkel Cell Carcinoma
fully humanized Mab (IgG1k). This Mab binds to pro- Merkel cell carcinoma is a rare aggressive cutaneous
grammed death ligand I (PD-L1) to prevent interaction malignancy caused by infection with polyoma virus
with receptors PD-1 and B7.1 (a costimulatory cell- and exposure to ultraviolet radiation. This cancer was
surface protein), reversing T-cell suppression. Activation classically treated with chemotherapeutic agents lead-
of B7.1 can potentially stimulate long-term responses ing to rare durable responses. Avelumab (Bavencio)
through development of new immunity via priming is a fully human Mab (IgG1l) with specificity to
and activation of T cells in lymph nodes. A lack of PD-L1. This Mab was approved by the FDA for
 CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies 261

treatment of Merkel cell carcinoma in 2017. Treatment Cutaneous squamous cell carcinoma
with this Mab increases response rates to about 50% Cemiplimab (Libtayo) is a human Mab (IgG4) for treat-
and extended durable response times approximately ment of cutaneous squamous cell carcinoma (CSCC)
five times.247,248 This Mab is in clinical trial to treat that is metastatic or locally advanced and not amenable
other solid tumors including but not limited to hepa- to surgery. CSCC is second only to basal cell carcinoma
tocellular, ovarian, esophagogastric, colorectal NSCLC, as the most common skin cancer. Surgical intervention
testicular, urothelial, and adrenocortical is not possible in 5% of patients. This Mab offers a treat-
carcinomas.249 ment with less morbidity than palliative radiation or
surgery, and gives an ORR in 50% of these otherwise
Neuroblastoma untreatable patients. There are many additional phase
Neuroblastoma is an aggressive tumor of children with II studies involving this Mab to be completed from
a 5-year survival of about 50%. Treatment classically is 2020 to 23.261,262
high-dose intensive chemotherapy, myeloablative
chemotherapy with stem cell rescue, and/or irradiation
therapy. Dinutuximab (Unituxin) is a chimeric Mab AUTOIMMUNE/INFLAMMATORY DISEASES
(IgG1k) with specificity to GD2 ganglioside that has Inflammatory Bowel Disease
mechanisms of action via CDC and ADCC. This Mab Inflammatory bowel disease (IBD) pathophysiology re-
is used in patients who have had at least a partial mains unknown but may have genetic, infectious, auto-
response to classic therapy.250,251 immune origins including cell-mediated immunity.
These diseases may be classified as ulcerative colitis
Glioblastoma Multiforme (UC), isolated to the colon, or Crohn’s disease primar-
GBM is the most common malignant primary brain tu- ily found in the colon but may involve the entire gastro-
mor in adults. This disease remains incurable. intestinal tract. With long-standing active disease,
Bevacizumab (Avastin) is FDA approved for treat- malignancy is much more frequent in UC than in
ment of recurrent GBM as salvage therapy. This medica- Crohn’s disease. Mild UC is treated with antiinflamma-
tion with chemotherapy increases overall survival by tory agents such as sulfasalazine and glucocorticoste-
4 months but as a single agent is not effective.252 roids. For more severe disease, high-dose steroids may
Relatlimab (BMS-986,016) is a human Mab (IgG4k) be used to maintain disease quiescent and low-dose ste-
with specificity to lymphocyte activation gene 3 (LAG3, roids to keep disease in remission. Low-dose chemo-
CD223) and is in phase I clinical trials to be completed therapeutic agent or immunosuppressive agent may
in 2020 for treatment of GBM.253 also be added if dose of corticosteroids is too high to
Tanibirumab (aka Olinvacimab, TTAC-0001) is a maintain remission. Surgery may be necessary to con-
human Mab (IgG1) with specificity to vascular endothe- trol disease. For Crohn’s disease, medical therapy is usu-
lial growth factor receptor-2 (VEFR-2) and is in phase II ally less successful in managing the disease and surgery
studies to treat GBM to be completed in 2020.254e256 may be necessary but is not curative as in UC. For both
of these disease processes, passive antibody therapy
Malignant Ascites may offer not only control of disease but possible com-
Catumaxomab (Removab) is a trifunctional rat/murine plete remission from mucosal damage.263,264
hybrid antibody (IgG2a/IgG2b). Catumaxomab con- Adalimumab (two formulations: Humira and Amje-
sists of one “half” (one heavy chain and one light chain) vita) is a recombinant human Mab (IgG1) with speci-
of an antiepithelial cell adhesion molecule (anti- ficity to tumor necrosis factor alpha (TNF-a). Both
EpCAM) antibody and one-half of an anti-CD3 anti- forms are FDA approved to treat Crohn’s disease as
body, so that each molecule of catumaxomab can well as multiple types of rheumatoid arthritis. In Crohn’s
bind both EpCAM and CD3. In addition, the Fc- disease, this medication decreases signs and symptoms
region can bind to an Fc receptor on accessory cells of disease and is able to induce clinical remissions.265,266
such as other antibodies, which has led to calling the Certolizumab (Cimzia) is a recombinant human-
drug a trifunctional antibody. This antibody’s mecha- ized m fragment with TNF-a as target. It is FDA
nism of action is through ADCC. It is approved for approved for both Crohn’s disease and Rheumatoid
use in Europe for malignant ascites from ovarian, arthritis.267e269
gastric, colon, pancreatic, breast, and endometrial carci- Vedolizumab (Entyvio) is a humanized Mab
noma and is a pending review for approval by the (IgG1k) that has selectivity for integrin a4b7 and is
FDA.257e260 FDA approved for treatment of Crohn’s disease. This
262 Immunologic Concepts in Transfusion Medicine

Mab mode of action is to selectively block trafficking of chemotherapy. Those with resultant hormone defi-
memory T cells into inflamed gut tissue by inhibiting ciencies are supplemented with hormones depleted by
a4b7-mucosal addressin cell adhesion molecule-1 the disease process. It is hoped that passive antibody
(MAd-CAM-1) interaction with intestinal vasculature. therapy will mitigate the sequelae of these inflammatory
This medication has shown a good safety profile with processes.
no cases of promyelocytic leukemia (PML), no
increased risk of infections, malignancies compared Plaque psoriasis/psoriatic arthritis
with classically treated IBD, and low incidence of Psoriasis affects 2%e3% of the world population and is
infusion-related reactions. This medication is also an inflammatory skin disease. Brodalumab (Siliz) is a
FDA approved for UC.270,271 human Mab (IgG2k) with specificity to IL-17 receptor
Infliximab (Remicade, Inflectra, Remsira) is a A (IL-17RA). It is FDA approved for treatment of plaque
chimeric Mab (IgG1k) with specificity to TNF-a and is psoriasis, and its mechanism of action is by inhibiting
FDA approved for IBD and multiple inflammatory IL-17A, IL-17F, IL-17C, IL-25, and IL-17A/F heterodimer
arthritic diseases. This medication allows for cytokine-induced responses including release of proin-
steroid-free remission within months of starting flammatory cytokines. When compared to ustekinu-
therapy.272 mab, response rates nearly doubled with brodalumab
Natalizumab (Tysabri) is a humanized Mab (IgG2k) in phase II and phase III trials during induction and
with selectivity to CD62L (L selectin a4 subunit of a4b1 maintenance therapies.275,276
and a4b7 integrins of leukocytes, not neutrophils, VLA- Other therapies currently also approved or being
4). This Mab is FDA approved for Crohn’s disease and studied for treatment of this disease include bermeki-
multiple sclerosis. This medications is effective in in- mab (MABp1,T2-18C3, CA-18C3, Xilonix), bimekizu-
duction of clinical remission in moderate-to-severe mab, briakinumab, certolizumab pegol (Cimzia),
Crohn’s disease. This medication does have the risk of etanercept (Enbrel), infliximab (Remicade, Inflectra,
PML.273,274 Remsima), itolizumab (Alzumab), adalimumab
Other Mab being studied for Crohn’s disease but not (Humira, Amjevita), ustekinumab (Stelara), secukinu-
yet approved by the FDA include Ustekinumab, brazi- mab (AIN457, Cosentyx), guselkumab (Tremfya),
kumab, etrolizumab, risankizumab, and ontamalimab. tildrakizumab (MK-3222, SCH-900,222, Ilumya, Ilu-
In contrast, Mabs studied but not beneficial for Crohn’s metri), risankizumab (ABBV-066, BI-655,066), miriki-
disease include andecaliximab, eldelumab, and fontoli- zumab (LY3074828), namilumab (MT203),
zumab. Refer to Table 16.1. netakimab, and vunakizumab. Refer to Table 16.1.
Withdrawn from market or ineffective for treating
Ulcerative Colitis psoriasis include efalizumab (Raptiva), fezakinumab,
Mabs being studied for UC but not yet approved by bleselumab, and teplizumab (MGA031, PRV-031,
the FDA include bimekizumab, etrolizumab, golimu- hOKT3g1(Ala-Ala)) Refer to Table 16.1.
mab, mirikizumab, ravagalimab, sacituzumab govite-
can, ontamalimab, and vatelizumab. Refer to Systemic juvenile idiopathic arthritis
Table 16.1. Abatacept (Orencia) is a recombinant soluble fusion
protein of the extracellular domain of human cytotoxic
Autoimmune Diseases T-lymphocyte-associated antigen 4 (CTLA-4) linked to
Autoimmune diseases affect many organs and tissues the modified Fc portion of human IgG1. Its mechanism
including liver, gall bladder, pancreas (b islet cells in dia- of action is as selective costimulation modulator as it in-
betes mellitus), nerve junctions (myasthenia gravis), hibits T lymphocyte activation by binding to CD80 and
thyroid, bone and joints, blood vessels, and multiorgan CD86, thereby blocking interaction with CD28. This
systems, systemic lupus erythematosus (SLE). Autoim- interaction provides a costimulatory signal necessary
mune arthritis is of multiple types including psoriatic, for full activation of T lymphocytes. This medication
sclerosis, rheumatoid arthritis (RA), and SLE. Many of is FDA approved for both juvenile idiopathic arthritis
these diseases are mediated by antibody or cellular (JIA) and adult RA.277e279
autoimmunity but ultimately appear to be secondary
to an underlying abnormality in T-cell immune- Rheumatoid Arthritis
regulatory control. These disease processes are historical- Certolizumab pegol alone or with methotrexate im-
ly controlled with antiinflammatory agents, immuno- proves quality of life in RA and may cause disease remis-
suppressive/immunomodulatory agents, or low-dose sion and reduce joint damage.280
TABLE 16.1
Summary of Monoclonal Antibody Therapies.
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
8H9 Iodine 124 monoclonal Antineoplastic Intravenous B7eH3
antibody Neuroblastoma, sarcoma,
(Murine) metastatic brain cancers
Another study Sloan Kettering
using I331 version phase I good
results

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Abagovomab Monoclonal antibody Antineoplastic Subcutaneous CA-125
(Murine) Phase II study for ovarian
An antiidiotypic mAb cancer
that mimics ovarian Phase III good immune
cancer CA125 protein response but no increase RFS
or OS no benefit
Abatacept Orencia Recombinant soluble Disease modifying Subcutaneous or Selective costimulation
FDA 2005 fusion protein of the Rheumatoid arthritis intravenous modulator, inhibits T cell
EU 2010 extracellular domain of Juvenile and adult psoriatic (T lymphocyte) activation
human cytotoxic T- arthritis (phase III) by binding to CD80 and
lymphocyte-associated CD86, thereby blocking
antigen 4 (CTLA-4) linked interaction with CD28.
to the modified Fc portion This interaction provides a
of human immunoglobulin costimulatory signal
G1 (IgG1). necessary for full
activation of T
lymphocytes.
Abciximab ReoPro Human-murine chimera Procedure modification Intravenous Platelet glycoprotein IIb/
c7Ec Fab FDA 1994 Recombinant mono High-risk coronary intervention IIIa receptor (CD41 7E3)/
EU 1995 clonal IgG1 Fab Platelet aggregation inhibitor Intergrin a-IIb
(country-specific
approval)
Abituzumab Humanized mono Antineoplastic Intravenous CD51 (?integrin alpha V)
DI17E6 clonal antibody IgG2k Colorectal cancer phase I
EMD525797 2013, phase II 2015 primary
endpoint PFS not met
Sclerosing interstitial lung
disease phase II terminated
2018 slow enrollment
Prostate phase IIno significant

263
increase PFS
Continued
TABLE 16.1

264
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Abrilumab Phase II study discontinued Integrin a-4 b-7
AMG 181 development (2016)
Actoxumab Human monoclonal Disease modifying Clostridium difficile
antibody Clostridium difficile toxin A
Phase I and II anti-CDTB1
much better
Adalimumab Humira Recombinant human IgG1 Disease modifying Injection TNF-a
FDA 2002 monoclonal antibody Humira subcutaneous
EU 2003 Rheumatoid arthritis;
Amjevita juvenile idiopathic arthritis;
FDA 2016 psoriatic arthritis; ankylosing
EU 2017 spondylitis; Crohn’s disease,
plaque psoriasis
Amjevita
Arthritis; juvenile rheumatoid
arthritis; psoriatic arthritis;
rheumatoid colitis; ulcerative
Crohn’s disease; psoriasis;
spondylitis; ankylosing
Possibly hemolytic disease of
newborn
Adecatumumab Recombinant human Antineoplastic Intravenous EpCAM (CD326) epithelial
MT-201 monoclonal antibody Breast phase Ibþ, colorectal cell adhesion molecule
IgG1k and prostate
Phase II completed
Phase III soon?
Aducanumab Human monoclonal Disease modifying Intravenous Beta-amyloid (N-terminus
antibody IgG1 Alzheimer’s disease 3e6) soluble oligomers
Phase III x 2 ongoing started and insoluble fibrils
2015
Afasevikumab Human monoclonal Disease modifying Subcutaneous IL17A and IL17F
antibody IgG1k Multiple sclerosis
Phase I completed
Nothing in pubmed
Afelimomab Murine F(ab’) Disease modifying TNF-a
Antibody Fab’ fragment Sepsis
IgG3k Phase III trial marginal benefit
abandoned
Alacizumab Humanized monoclonal Limited information on VEGFR2
pegol antibody F(ab’)2 development;
Cancer
Alemtuzumab Lemtrada Humanized rat Antineoplastic Intravenous CD52
LDP-03 FDA 2014 monoclonal antibody B-Cell CLL, CTCL, T cell
Campath-1H EU 2013 IgG1k lymphoma
MS Disease modifying
Campath Multiple sclerosis (phase III)
FDA 2001 Not effective for kidney
EU 2001 transplant conditioning or
CLL rejection prevention
Alirocumab Praluent Human monoclonal Disease modifying Subcutaneous Proprotein convertase

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

FDA 2015 antibody IgG1 Decrease cholesterol subtilisin kexin type 9
EU 2015 Phase III (PCSK9)
Altumomab Hybri-ceaker Murine monoclonal Diagnostic purpose radiology CEA
pentetate In98 antibody IgG1 colorectal cancer (diagnosis)
ALX-0171 Trimeric nanobody Antiinfectious Inhalation RSVF
RSV phase II 2020
Amatuximab Chimeric murine-human Antineoplastic Intravenous Mesothelin
MORAb-009 monoclonal antibody Ovarian cancer Prohibits binding of MSLN
IgG1k Phase II with antigen CA125/
Now research on using to treat MUC16
mesotheliomas
Phase I/II
Pancreatic cancer
AMG330 Bispecific T-cell engager Antineoplastic Intravenous CD33 and CD3
(BiTE) AML phase I AML 2020
Anatumomab Murine monoclonal Antineoplastic Tumor-associated
mafenatox fragment Fab Nonsmall cell lung carcinoma glycoprotein 72 (TAG-72)
Andecaliximab Chimeric monoclonal Antineoplastic gastric cancer Intravenous Gelatinase B is a matrix
GS 5745 antibody IgG4k phase I, II, III ongoing or metalloproteinase-9
gastroesophageal junction (MMP-9)
adenocarcinoma phase III
ongoing
Crohn phase II no response,
UC
Anetumab Human monoclonal Antineoplastic ovarian phase Mesothelin
ravtansine antibody IgG1l II, lung, pancreatic phase I, Prohibits binding of MSLN
In98 breast now research on using with antigen CA125/
to treat mesotheliomas MUC16

265
Phase II
Cervical cancer ?preclinical
Continued
 266
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Anifrolumab Human monoclonal Disease modifying Intravenous Interferon a/b receptor
antibody IgG1k Systemic lupus erythematosus
phase I and IIb 2018
Anrukinzumab Humanized monoclonal Disease modifying IL-13
(¼IMA-638) antibody IgG1k Asthma phase II ?results
UC phase II no benefit
Apolizumab Humanized monoclonal Antineoplastic non-Hodgkin’s HLA-DRb
antibody lymphoma abandoned 2009
toxic effects
2009 CLL phase I/II
Arcitumomab CEA-Scan Murine monoclonal Diagnostic imaging CEA
FDA 1996 antibody IgG1 Fab’ Gastrointestinal cancers
EU 1996 Colorectal cancers
Withdrawn EU
market 2005
Ascrinvacumab Human monoclonal Antineoplastic mesothelioma Activin receptor-like
antibody Nothing in pub med or web kinase 1
search
Aselizumab Humanized monoclonal Disease modifying L-selectin (CD62L)
antibody Severe injured patients phase
II 2004, no benefit
Atezolizumab Tecentriq Fc engineered, humanized Antineoplastic agent, treat Intravenous Binds to PD-L1 and
MPDL3280A FDA 2016 monoclonal antibody metastatic urothelial blocks interactions with
IgG1k carcinoma, non-small cell the PD-1 and B7.1
lung cancer receptors FDA-approved
Phase III atezolizumab
Bladder/urothelial cancer (TECENTRIQ, Genentech,
phase I Inc.), in combination with
Breast cancer phase Ib triple bevacizumab, paclitaxel,
marker neg breast cancer and carboplatin for the
first-line treatment of
patients with metastatic
nonsquamous, nonsmall
cell lung cancer (NSq
NSCLC) with no EGFR or
ALK genomic tumor
aberrations
Atidortoxumab Human monoclonal Limited information on use and Negative search PubMed- Staph aureus alpha toxin
antibody IgG1k development internet
Atinumab Human monoclonal Disease modifying RTN4
antibody IgG4k Acute spinal cord injury
Atorolimumab Developed?? Human monoclonal Disease modifying hemolytic Rhesus factor
antibody IgG3 disease of the newborn
Avelumab Bavencio Human monoclonal Antineoplastic Intravenous PD-L1
FDA 2017 antibody IgG1l Cancers, ovarian, gastric,
nonsmall cell lung (NSCLC),
metastatic, solid tumors
phase II

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Studies completed metastatic
Merkel cell carcinoma
Azintuxizumab Chimeric/humanized Antineoplastic CD319
vedotin monoclonal antibody IgG1 Nothing in PubMed
BAN-2401 Humanized monoclonal Disease modifying Alzheimer A Intravenous Soluble Ab amyloid
antibody IgG1 phase IIb study ongoing protofibrils
started 2013
Bapineuzumab Humanized IgG1 Disease modifying Intravenous Beta amyloid
monoclonal antibody Alzheimer’s disease Fibrillary and soluble b
Phase III no more studies amyloid
discontinued research 2012
ARIA-E, amyloid-related
imaging abnormalitieseedema
Basiliximab Simulect Chimeric monoclonal Immunosuppressive agents Intravenous CD25 (a chain of IL-2
FDA 1998 antibody IgG1k Prophylaxis of acute receptor)
EU 1998 rejection in allogeneic renal
transplantation
Bavituximab Chimeric monoclonal Cancer, viral infections (Hep C) Phosphatidylserine
antibody IgG1k phase III NSCLC failed to
IgG3 (SUNRISE trial) improve survival Sunrise trial
stopped Feb 2016, phase II/III
breast cancer, phase II
pancreatic cancer, phase I/II
trial hepatocellular carcinoma,
phase I malignant
melanoma þ rectal cancer
good response rectal; not for
prostate cancer, phase II
hepatitis C not resulted?

267
Continued
 268
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
BAY-103356 Humicade Humanized monoclonal For research only TNF a
CDP 571 Senlizumab antibody IgG4k Phase II 1995
BCD-100 Human monoclonal Antineoplastic Intravenous Programmed cell death-1
antibody Phase II/III melanoma (PD1)
NCT03269565 (complete Dec
2019)
Bectumomab LymphoScan Fab’-IgG2k Antineoplastic CD22
Non-Hodgkin’s lymphoma
(detection)
Begelomab Begedina Murine IgG2b Disease modifying GvHD DPP4 binds CD26 on T
phase II/III lymphocytes
Belantamab Humanized monoclonal Antineoplastic No studies or info on BCMA
mafodotin antibodymab clinical trial, PubMed, FDA
substance
Belatacept Nulojix Soluble fusion Immunosuppressive agents Intravenous Selectively inhibits T-cell
FDA 2011 Protein consisting of the Prophylaxis renal transplant activation through
modified extracellular rejection in adults costimulation blockade
domain of CTLA-4 fused Phase III binds to both CD80 and
to Fc domain of a FDA approved CD86 blocking CD28
recombinant human
monoclonal antibody IgG1
Belimumab Benlysta Human monoclonal Disease modifying Intravenous B-cell activating factor
FDA 2011 antibody IgG1l Kidney transplant phase II Subcutaneous (BAFF), B-lymphocyte
EU 2011 Treat SLE (testing phase III for stimulator
LymphoStat-B renal involvement)
Phase II Rheum arthritis failure
Phase II Srogren 
GVHD ongoing
Bemarituzumab Humanized monoclonal Antineoplastic FGFR2
antibody
Benralizumab Fasenra Humanized monoclonal Disease-Modifying Subcutaneous Interleukin-5 (IL-5a)
FDA 2017 antibody IgG1k Asthma phase III completed receptor alpha subunit-
EU 2017 Severe asthma eosinophilic directed cytolytic (CD125)
subtype
Berlimatoxumab Human monoclonal Staph aureus bicomponent No studies clinical, no find
antibody leukocidin creative, zero pub med
Bermekimab Xilonix Human monoclonal Disease modifying psoriasis Subcutaneous IL17A
MABp1 antibody IgG1k phase III x2 2020 Intravenous
T2-18C3 Ank spond II 2022
CA-18C3 Psor arth II 2020 III 2020
Bersanlimab Human monoclonal ICAM-1
antibody

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Bertilimumab CAT-214 Human monoclonal Disease modifying Intravenous CCL11 (eotaxin-1)
antibody IgG4k Severe allergic disorders
phase II atopic dermititis
Ongoing studies bullous
pemphigoid and ulcerative
colitis phase II
Besilesomab Scintimun Murine monoclonal Diagnostic use CEA-CAM8-related
EU 2010 antibody IgG1k Inflammatory lesions and antigen
Not FDA metastases (detection)
approved
Bevacizumab Avastin Humanized monoclonal Antineoplastic agent Intravenous solution or VEGF-A anti-
FDA 2004 antibody IgG1k Antiangiogenesis inhibitor ophthalmic injection angiogenesis inhibitor
EU 2005 BiTE Colorectal cancer 2004, May not be so good for
NSCLC 2006, RCC 2009, GBM or ovarian
GBM phase III, ovarian
cancer, metastatic cervical
cancer, fallopian 2014
Breast cancer (FDA removed
approval for breast cancer
2010)
Recurrent glioblastoma
multiform
Nonsquamous nonsmall cell
lung cancer
Bezlotoxumab Zinplava Human monoclonal Disease modifying phase III Intravenous Clostridium difficile colitis
FDA 2016 antibody IgG1 studies done MODIFY I and II anti-B toxin
EU 2017 Modify III ongoing
Pseudomembranous colitis
Continued

269
 270
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Biciromab FibriScint Murine monoclonal Detect cardiovascular Fibrin II, beta chain
fragment Fab’ IgG1k thromboembolism (diagnosis)
Bimagrumab Human monoclonal Disease modifying Intravenous Activin A receptor type IIB
BYM338 antibody IgG1l Myostatin inhibitor (ACVR2B)
DM II decrease BMI phase II
Sporadic inclusion body
myositis phase III not meet
endpoint
Treat sarcopenia in older
adults phase II
Bimekizumab Humanized monoclonal Disease modifying Subcutaneous IL 17A and IL 17F
antibody IgG1k Ankylosing spondylitis (2018 II,
2022 II, þ), plaque psoriasis
(2021 III, 2020 III, 2019 III, þ),
psoriatic arthritis (2020), RA
(2017 II), UC phase II
Bivatuzumab Humanized monoclonal Antineoplastic squamous cell CD44 v6
mertansine antibody IgG1 carcinoma, breast phase I fail
x2, head/neck or esophagus
phase I fail, toxicity
Bleselumab Human monoclonal Disease modifying organ Intravenous CD40
antibody IgG4k transplant rejection phase II
2020 to prevent FSGS in
kidney transplant patients
Phase II psoriasis- medication
tolerated with minimal
reaction, no benefit to disease
process
Blinatumomab Blincyto Murine(scFv - kappa - Antineoplastic Intravenous Bispecific T-cell engager
FDA 2014 heavy) - (scFv - heavy - Ph chrom neg pre-B ALL monoclonal antibody
EU 2015 kappa) BiTE (CD19þ) phase II construct that directs CD-
B-cell precursor acute 3 positive effector
lymphoblastic leukemia memory T cells to CD19-
(ALL) initial or relapsed/ positive target cells
refractory
Blontuvetmab Blontress Canine monoclonal Veterinary treat canine B-cell CD20
antibody IgG2 k/l lymphoma
Blosozumab Humanized IgG4k Disease modifying Intravenous SOST
Osteoporosis 3 phase I and Subcutaneous Antisclerostin
one phase 2 injection site
reaction and antibodies to
antibody
Bococizumab Humanized IgG2k Disease modifying Subcutaneous Neural apoptosis-
RN316 Dyslipidemia intravenous regulated proteinase 1
PF-04950615 Phase III 2019 PCSK9 (proprotein
Discontinued secondary to convertase subtilisin/
antidrug antibodies, no kexin type 9, neural
primary endpoint achieved apoptosis-regulated

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

convertase 1, NARC1,
NARC-1, proproteine
convertase 9, PC9)
Brazikumab Human monoclonal Disease modifying Subcutaneous IL23
antibody IgG2l Ulcerative colitis phase II 2021
Phase I/II completed Crohn.
Phase III ongoing
Brentuximab Adcetris Chimeric humanized Antineoplastic Intravenous CD30 (TNFRSF8) an
vedotin FDA 2013 monoclonal antibody Hodgkin lymphoma antibody-drug conjugate
Breakthrough IgG1k Anaplastic large-cell (ADC) 3 parts: anti-CD30
therapy status lymphoma (cAC10, a cell membrane
by FDA 2018 protein of the tumor
necrosis factor receptor),
a microtubule disrupting
agent monomethyl
auristatin E (MMAE) and a
protease-cleavable linker
that attaches MMAE
covalently to cAC10. The
combination disrupts the
intracellular microtubule
network causing cell-
cycle arrest and apoptotic
cellular death
Briakinumab Human monoclonal Disease modifying psoriasis, Intravenous IL-12, IL-23
antibody Drug development stopped for
psoriasis, phase IIb study in
Crohn’s
Brodalumab Siliz Human monoclonal Disease modifying Subcutaneous Receptor IL-17RA
AMG827 FDA 2016 antibody IgG2k Plaque psoriasis

271
Completed phase III
Continued
TABLE 16.1

272
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Brolucizumab FDA review 2018 Humanized single chain Disease modifying Intravitreal VEGFA
RTH258 antibody fragment (scFv k) Wet or age-related macular [Link]
ESBA1008 degeneration phase III to be com/news/media-
completed Sept 2018, 2020 releases/new-novartis-
HAWK (NCT02307682) and phase-iii-data-
HARRIER (NCT02434328) brolucizumab-
phase III trials good results demonstrate-reliability-
12-week-treatment-
interval
Brontictuzumab Humanized IgG2l Antineoplastic Intravenous Notch 1
Phase I
Colorectal
Lymphoid
Adenoid cystic
Solid tumors
Burosumab Crysvita Human monoclonal Disease modifying Subcutaneous FGF 23 phosphaturic
KRN23 FDA 2018 antibody IgG1k X-linked hypophosphatemia [Link] hormone fibroblast
Phase III completed [Link]/ growth factor 23
[Link]
Cabiralizumab Humanized monoclonal Antineoplastic metastatic Intravenous CSF1R
antibody IgG4k pancreatic cancer phase II
2020
Many other cancers phase I
Camidanlumab Human monoclonal Antineoplastic Intravenous CD25
tesirine antibody B-cell Hodgkin’s lymphoma,
ADCT-21 non-Hodgkin lymphoma,
acute lymphoblastic leukemia,
acute myeloid leukemia 2018
phase I
Advanced solid tumors with
literature evidence of CD25(þ)
treg content
Head and neck
Nonsmall cell lung
Gastric, esophageal,
Pancreas, bladder,
Renal cell, melanoma,
Triple-negative breast, ovarian
phase I 2021
Sinilimab China pending Humanized monoclonal Antineoplastic Programmed cell death 1
Camrelizumab approval antibody IgG4k Phase III nasopharyngeal (PDCD1)
IBI308 cancer 2021
Phase III esophageal cancer
2021
Canakinumab Ilaris Human monoclonal Disease modifying Subcutaneous IL-1b
ACZ885 FDA 2009 antibody IgG1k Cryopyrin-associated
EU 2009 periodic syndromes
Including familial cold auto-

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

inflammatory syndrome and
MuckleeWells syndrome;
tumor necrosis factor
receptor-associated
periodic syndrome (TRAPS);
hyperimmunoglobulin D
syndrome (HIDS)/
mevalonate kinase
deficiency (MKD) and familial
Mediterranean fever (FMF)
Systemic Juvenile idiopathic
arthritis
Treat Juvenile idiopathic
arthritis phase III
NSCLC 2025 phase III
CVD rejected by FDA
Behcet
Cantuzumab Humanized monoclonal Antineoplastic Intravenous Mucin CanAg
mertansine antibody IgG1k Colorectal cancer phase I 2007
Cantuzumab Humanized monoclonal Antineoplastic MUC1
ravtansine antibody IgG1k Cancers
Caplacizumab- Cablivi Humanized single variable Disease modifying Intravenous VWF
yhdp (Nanobody domain antibody (bivalent Inhibits interaction vWF and Subcutaneous
program) nanobody) platelets
FDA 2019 Treat acquired TTP
EU 2018 Phase III Hercules study
completed
Continued

273
TABLE 16.1

274
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Capromab Prostascint Murine monoclonal Diagnostic imaging Intravenous Tumor surface antigen
pendetide FDA 1996 antibody Prostatic carcinoma cells PSMA
detection
Carlumab Human monoclonal Antineoplastic Intravenous hMCAF/MCP-1 (human
antibody IgG1k Prostate phase II no long term macrophage/monocyte
benefit chemotactic protein-1)
Pulm fibrosis phase II no
benefit
Carotuximab Chimeric monoclonal Antineoplastic angiosarcoma Intravenous Endoglin (CD105)
TRC105 antibody IgG1k Hepatocellular car phase I/II
2020
Glioblastoma multi-phase II
2014 terminated poor accrual
?results
Angiosarcoma phase III 2019
TAPPAS trial
Prostate ca phase II 2021
NSCLC phase I 2019
Catumaxomab Removab Removab: A trifunctional Antineoplastic Intraperitoneal EpCAM, CD3
FDA approved rat/murine hybrid antibody Removab Catumaxomab consists
pend 2017) IgG2a/IgG2b Ovarian cancer phase II, of one “half” (one heavy
EU approved malignant ascites phase II, chain and one light chain)
2009 gastric cancer phase II of an anti-EpCAM
(ovarian, gastric, colon, antibody and one half of
pancreatic, breast, an anti-CD3 antibody, so
endometrial) that each molecule of
Proxinium catumaxomab can bind
Head and neck cancer both EpCAM and CD3. In
addition, the Fc-region
can bind to an Fc receptor
on accessory cells like
other antibodies, which
has led to calling the drug
a trifunctional antibody.
cBR96- Humanized monoclonal Antineoplastic
doxorubicin antibody IgG1k Cancer
immuno- Sponsorship ceased 2005
conjugate
aka SGN-15
Cedelizumab CIMZIA Humanized monoclonal Prevent organ transplant CD4
antibody IgG4k rejection
Cemiplimab Libtayo Human monoclonal Antineoplastic Intravenous Programmed cell death
FDA 2018 antibody IgG4 Nonsmall cell lung cancer receptor PCDC1
(NSCLC) phase I 2021, phase
III 2022  3
Oropharynx phase II 2022
Multiple myeloma phase II
2022

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Ovarian ca phase II 2022
Head neck squamous cell
carcinoma phase II 2020
Cutaneous squamous cell
Glioblastoma multiforme
phase II 2021
Lung ca phase II 2022
Cervical cancer phase III 2023
Cergutuzumab Humanized monoclonal Antineoplastic phase I Dec Intravenous IL2
amunaleukin antibody 2018
Aka RO6895882,
CEA-IL2v
Certolizumab Cimzia Recombinant, humanized Disease-Modifying Subcutaneous Tumor necrosis factor a
pegol FDA 2008 antibody Fab’ fragment Crohns blocker
CDP870 EU 2009 Rheumatoid arthritis (phase
IIIs completed)
Psoriatic arthritis phase III
Ankylosing spondylitis
Cetrelimab Relatimab Human monoclonal Antineoplastic Nothing on PubMed or Programmed cell death 1
antibody IgG4k creative lab
Substance is registered
with FDA
Cetuximab Leukeran Recombinant chimeric Antineoplastic agent Intravenous solution EGFR
IMC-225 Erbitux monoclonal antibody Metastatic colorectal cancer
FDA 2004 IgG1k and head and neck cancer
EU 2004 NSCLC
Citatuzumab Humanized Fab IgG1k Antineoplastic ovarian cancer Study phase I terminated EpCAM
bogatox and other solid tumors 2008
Continued

275
 276
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Cixutumumab Human monoclonal Antineoplastic Intravenous IGF-1 receptor (CD221)
antibody IgG1k Solid tumors
Sarcoma phase II
Esophageal cancer phase II
Rhabdomyosarcoma phase II
no benefit
Liver cancer phase I
Low antitumor effect
Pancreas no benefit 2012
Clazakizumab Humanized monoclonal Disease modifying rheumatoid Subcutaneous IL6
ALD518 antibody arthritis phase II 2015  3
Crohn disease phase II 2013
Highly sensitized renal
transplant candidates phase II
2020
Treat post-tx rejection kidney
phase II 2020
Antibody-mediated rejection
phase III 2027
Clenoliximab Chimeric monoclonal Disease modifying Rheum Arth CD4
antibody No study since 2003
Clivatuzumab hPAM4-Cide Humanized monoclonal Antineoplastic MUC1
tetraxetan antibody IgG1k Pancreatic cancer
(90)Y- Phase III 2017 PANCRIT-1
clivatuzumab study. Study terminated no
tetraxetan increase improvement of
overall survival
Codrituzumab Humanized monoclonal Antineoplastic Glypican 3
antibody IgG1k HCC
Phase Ib no response
Phase II no response
Cofetuzumab Humanized monoclonal Antineoplastic Nothing on PubMed or Protein tyrosine kinase 7
pelidotin antibody IgG1k creative lab (PTK7)
Substance is not
registered with FDA
Coltuximab Chimeric monoclonal Antineoplastic CD19
ravtansine antibody IgG1 conjugated Relapse/refractory ALL phase
SAR3419 to DM4 (N20 -(4-((3- II 2015 low clinical response
carboxypropyl)dithio)-4- Phase II moderate response
methyl-1-oxopentyl)-N20 -
deacetylmaytansine)
Conatumumab Human monoclonal Antineoplastic Intravenous TRAIL-R2
AMG655 antibody IgG1k Phase II 2019: Advanced solid
tumors
Carcinoid

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Colorectal cancer
Locally advanced
Lymphoma
Metastatic cancer
Nonsmall cell lung cancer
Sarcoma
Solid tumors
Colon cancer phase Ib/II no
benefit
Concizumab Humanized IgG4k Disease modifying Subcutaneous Kunitz-type protease
Hemophilia A and B phase II inhibitor 2 domain of
2020 tissue factor pathway
inhibitor (TFPI)
Cosfroviximab ZMapp Chimeric monoclonal Disease modifying Ebola virus Ebola virus glycoprotein
antibody IgG1k Ongoing studies show benefit
Triple monoclonal but not enough enrolled to
antibody cocktail power study
Crenezumab Humanized monoclonal Disease modifying Intravenous 1-40-b-amyloid
RG7412 antibody IgG4 Alzheimer’s disease phase III
MABT5102A study ongoing prodromal/mild
AD 2021
Phase III 2022
Crizanlizumab FDA review Humanized monoclonal Disease modifying Intravenous P Selectin
SelG1 possible 2019 antibody IgG2k Sickle cell disease phase II
2022 children
Phase II adults decrease pain
crisis
Crotedumab Human monoclonal Disease modifying DM type II No results GCGR
antibody IgG4k

277
Continued
 278
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Cusatuzumab Humanized monoclonal Antineoplastic Intravenous CD70
ARGX-110 antibody IgG1 Phase I completed safe
Phase I/II CTCL dec 2018
Nasopharyngeal carcinoma
2018
Dacetuzumab Humanized monoclonal Antineoplastic Intravenous CD40
HU-S2C6 antibody IgG1 Hematologic cancers
ASKP1240 Multiple myeloma phase I 2007
SGN-40 Large B-cell lymphoma phase
II 2009 enrollment stopped no
benefit
CLL phase II 2006
NHL phase I
Renal transplant (CIRRUS I)
phase II 2022
SLE nephritis phase II 2020
Daclizumab Zenapax Humanized monoclonal Disease modifying CD25 (a chain of IL-2
Zinbryta antibody IgG1k Prevention of organ transplant receptor)
FDA 1997 rejections
EU 1999 Phase IV kidney transplants,
Zenapax multiple sclerosis phase III
withdrawn from 2018 pulled from market
market Apr 2009 secondary inflammatory brain
for commercial disorders Biogen
reasons Heart transplant phase IV 108
Zinbryta studies Zanapax discontinued
withdrawal 2018 from market by Roche
secondary to (basiliximab replace)
risk/benefit
profile
Dalotuzumab Humanized monoclonal Antineoplastic Intravenous IGF-1 receptor (CD221)
antibody IgG1k Phase I multiple
Phase II breast no
improvement  2
Phase III colon no
improvement
Ped solid phase I
Dapirolizumab Humanized monoclonal SLE phase II Nov 2018 Intravenous CD154 (CD40L)
pegol antibody IgG1k Phase I safe
Daratumumab Darzalex Human IgG1k Antineoplastic agent Intravenous solution CD38
FDA 2015 Multiple myeloma relapse/ Induces CDC, ADCC,
EU 2016 refractory ADCP, and apoptosis
Phase III completed
Dectrekumab Human monoclonal Cancers, asthma phase II, Nothing on PubMed IL-13
QAX576 antibody IgG1k idiopathic pulmonary fibrosis, Substance is registered
eosinophilic Esophagitis phase with FDA, creative lab

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

II some benefit but primary
endpoint not achieved,
Keloids, Crohn’s disease
phase II trials 2013
Demcizumab Humanized monoclonal Antineoplastic Intravenous Delta-like ligand 4DLL4
antibody IgG2k NSCLC phase II 2018 DLL4 and Notch1,
Phase I safety established with signaling stimulated by
50% tumor regression DLL4 plays a role in
response development of blood
vessels throughout life
Denintuzumab Humanized monoclonal Antineoplastic Intravenous CD19
mafodotin antibody IgG1k LBCL phase II terminated
HBU-12 Antibody-drug conjugate study by company
SGN-CD19A (ADC) composed of a Acute lymphoblastic leukemia
humanized anti-CD19 and B-cell non-Hodgkin
monoclonal antibody lymphoma
conjugated to the Phase I 2017
microtubule-disrupting Phase II 2018 terminated by
agent monomethyl sponsor
auristatin F (MMAF)
Denosumab Prolia Human monoclonal Disease modifying Subcutaneous Receptor activator of
AMG162 FDA 2010 antibody IgG2 Osteoporosis FREEDOM trial, nuclear factor kappa-B
EU 2010 bone metastases, etc. 186 ligand (RANKL)
Xgeva studies Xgeva: Prevention of
FDA 2011 Phase III completed skeletal-related events
EU 2011 Melanoma phase II 2022 (SREs) in adults with bone
Bone giant cell tumor phase II metastases from breast
2025 and castration-resistant
prostate cancer.
Prolia: Osteoporosis

279
Continued
 280
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Depatuxizumab Chimeric humanized Glioblastoma Intravenous EGFR
mafodotin monoclonal antibody Phase III Nov 2019
ABT 414 IgG1k CONJUGATED TO Children phase III 2020
AURISTATIN F
Derlotuximab Chimeric monoclonal Immunoassays Histone complex
biotin antibody IgG1k Potential for glioblastoma
Iodine (131 I) multiforme
derlotuximab
biotin
Detumomab Murine monoclonal Antineoplastic Nothing on PubMed or CD3E
antibody IgG1 B-lymphoma cell clinical trials
Substance is not
registered with FDA, is on
creative lab
Dezamizumab Humanized monoclonal Disease modifying Intravenous Serum amyloid P
GSK-2398852 antibody IgG1k Treat amyloidosis component
Transthyretin cardiomyopathy
amyloidosis (ATTR-CM),
suspended pending data
review Aug 2018 phase I x 4
Dinutuximab Unituxin Chimeric monoclonal Antineoplastic Intravenous GD2 ganglioside
APN311 FDA 2015 antibody IgG1k Neuroblastoma phase I 2022
EU 2015 then SCLC phase III Nov 2019
withdrawn EU Osteosarcoma phase II Dec
2018
Neuroblastoma phase II 2020
Diridavumab Human monoclonal Disease modifying Intravenous Influenza A hemagglutinin
CR6261 antibody IgG1l Infectious disease/influenza A
Very good response in animal
study mice
Phase II 2019
Domagrozumab Humanized monoclonal Disease modifying GDF-8
PF-06252616 antibody IgG1k Duchenne muscular dystrophy
phase II 2018
Phase I completed
Dorlimomab F(ab’)2 Murine Nothing on PubMed or
aritox clinical trials
Substance is not
registered with FDA, or
creative lab
Dostarlimab FDA review Humanized monoclonal Antineoplastic Programmed cell death
TSR042 pending 2019 antibody IgG4k Solid tumor protein-1 (CD279) PCDP1
WBP285 Phase I, II, III studies ongoing
Ovarian CA (first study) phase
III 2023
Drozitumab Human monoclonal Antineoplastic Intravenous Death receptor 5 (DR5)

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

PRO95780 antibody IgG1l Colorectal cancer Ib 2012
rhuMAB DR5 Preclinical
rhabdomyosarcoma 2018
Chondrosarcoma not
efficacious
NHL results?
Duligotuzumab Human monoclonal Antineoplastic squamous head Anti-EGFR  Anti-HER3
MEHD7945A antibody IgG1k and neck phase II no benefit bispecific antibody
Colon ca phase II no benefit
Dupilumab Dupixent Human monoclonal Disease modifying asthma, Subcutaneous IL4
FDA 2017 antibody IgG4 atopic dermatitis
Ongoing studies
Durvalumab Imfinzi Human monoclonal Antineoplastic agent Intravenous PD-L1 (CD274) and
FDA 2017 antibody IgG1k Treat NSCLC stage III phase I, CD80dinhibit binding of
urothelial carcinoma programmed death ligand
1 to PD-1 and CD80
allowing T cell to
recognize and kill tumor
cells
Dusigitumab Human monoclonal Antineoplastic Intravenous ILGF2
MEDI 573 antibody IgG2l Breast cancer phase II results?
HCC phase II results?
Duvortuxizumab Chimeric/humanized Antineoplastic Intravenous CD19, CD3E
MGD011 monoclonal antibody B-cell malignancy
Phase I/II Jul 2018/2020
Ecromeximab Chimeric monoclonal Antineoplastic Intravenous GD3 ganglioside
KW2871 antibody IgG1k Metastatic melanoma
Phase I/II clinical activity
limited

281
Continued
TABLE 16.1

282
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Eculizumab Soliris Humanized monoclonal Immuno-regulation Intravenous C5
PNH antibody IgG1/4 Paroxysmal nocturnal
FDA 2007 hemoglobinuria (PNH),
EU 2007 atypical hemolytic uremic
aHUS, and syndrome (HUS)
myasthenia Generalized myasthenia
gravis gravis (MG)
FDA 2018 Phase II CAD
EU 2018
Japan 2018
Edobacomab Murine monoclonal No improved survival Endotoxin
E5 antibody
Edrecolomab Panorex Murine monoclonal Antineoplastic Intravenous Glycoprotein EpCAM/17-
antibody IgG2k Colorectal carcinoma phase III 1A
2003 no improvement
Efalizumab Raptiva Recombinant humanized Disease modifying Subcutaneous Human CD11a
FDA 2003 monoclonal antibody (2003 approved) psoriasis Voluntary withdrawal Increase risk progressive
EU 2004 IgG1k 2009 multifocal
Withdrawn both leukoencephalopathy
markets 2009 (PML)
Efungumab Mycograb Human scFv Antiinfectious agent Intravenous Heat shock protein 90
MYC123 Mycograb C28Y Invasive Candida infection (Hsp90)
Eldelumab Human monoclonal Crohn’s disease phase IIa no Intravenous Interferon g-induced
Mdx 1100 antibody IgG1k significant response, ulcerative protein
colitis phase IIb prim endpoint CXCL 10
not achieved
Rheum arthritis phase II
Elezanumab Human monoclonal Spinal cord injury and multiple Intravenous REPULSIVE GUIDANCE
PR-1432051 antibody IgG1l sclerosis phase II 2021 MOLECULE FAMILY
ABT-555 MEMBER A (RGMA)
Elgemtumab Human IgG1k Antineoplastic Intravenous ERBB3 (HER3)
LJM716 Breast gastric phase I
Elotuzumab Empliciti Human IgG1k Antineoplastic Intravenous SLAMF7
PDL063 FDA 2015 Multiple myeloma
EU 2016 Phase III completed and
ongoing
Elsilimomab Humanized monoclonal Antineoplastic multiple IL-6
B-E8 antibody IgG1 myeloma
Not effective in mice
Emactuzumab Humanized monoclonal ANTINEOPLASTIC HUMAN MACROPHAGE
RG7155 antibody IgG1 Phase I 2019 solid tumors COLONY-STIMULATING
Phase II 2025 REDIRECT study FACTOR RECEPTOR
ovarian, fallopian tube cancer (CSF1R, CD115)
Pancreatic phase II 2020
Emapalumab Gamifant Human monoclonal Hemophagocytic Intravenous Interferon g
NI-0501 FDA 2018 antibody IgG1l lymphohistiocytosis
EU pending Phase III 2021

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Emibetuzumab Humanized monoclonal Antineoplastic Intravenous Hepatocyte growth factor
LA480 antibody IgG4k NSCLC phase II 2020 receptor (HHGFR) and
LY2875358 Bivalent antibody Advanced cancer MET signaling
Gastric safe ?effective
adenocarcinoma
Gastroesophageal junction
adenocarcinoma
Hepatocellular cancer
Renal cell carcinoma
Nonsmall cell lung cancer
phase II Jan 2018
Phase I safe with tumor
response
Emicizumab Hemlibra Humanized monoclonal Disease modifying Subcutaneous Activated F9, F10
ACE910 FDA 2018 antibody IgG4k Hemophilia A phase III 2020
Bispecific With or without inhibitors
Enapotamab Human monoclonal Antineoplastic Nothing on PubMed or Human growth factor
vedotin antibody IgG1k clinical trials receptor AXL
Substance is not
registered with FDA, or
creative lab
Enavatuzumab Humanized monoclonal Antineoplastic Intravenous TWEAK receptor
PDL192 antibody IgG1k Phase I 2011
No responses and liver
pancreatic toxicity
Enfortumab FDA review Human monoclonal Antineoplastic bladder cancer Nectin-4
vedotin pending 2019 antibody phase I Anti-Nectin-4
Phase II ongoing Monoclonal antibody
attached to a
microtubule-disrupting

283
agent, monomethyl
auristatin E (MMAE)
Continued
TABLE 16.1

284
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Enlimomab Murine monoclonal Disease modifying Nothing on PubMed or ICAM-1 (CD54)
pegol antibodyIgG2a Stroke clinical trials
Substance is not
registered with FDA
Enoblituzumab Humanized monoclonal Antineoplastic CD276 (B7eH3)
MGA 271 antibody IgG1k Phase I 2022 children
Neuroblastoma
Rhabdomyosarcoma
Osteosarcoma
Ewing sarcoma
Wilms tumor
Desmoplastic small round cell
tumor
Phase I melanoma, NSCLC
2018
Phase II prostate 2021
Enokizumab Humanized monoclonal Asthma phase II Intravenous IL9
MEDI528 antibody IgG1k No improvement
Enoticumab Human monoclonal Antineoplastic Delta-like canonical notch
REGN421 antibody IgG1k Phase 1 2014 ovarian cancer þ ligand 4 (DLL4)
Ensituximab Chimeric monoclonal Antineoplastic Intravenous 5AC
NEO-201 antibody IgG1k Phase II pancreatic and
NPC-1C colorectal cancer 2017
Enterecept Enbril 1-235-Tumor necrosis Disease modifying Subcutaneous TNFa
RHU-TNFR:FC FDA 2003 factor receptor fusion Antirheumatic drug
protein attached to Not effective for inflammatory
recombinant human IgG1 bowel disease
Fc fragment
Epitumomab Sontuzumab Humanized monoclonal Antineoplastic Episialin
cituxetan antibody IgG1 Breast cancer phase II 2012 no MS4A1 (membrane-
AS-1402 benefit spanning 4-domains
HuHMFG-1 subfamily A member 1,
CD20 (HMFG-1)
Epratuzumab Humanized monoclonal Antineoplastic Intravenous CD22
HLL2 antibody IgG1k B-ALL phase III ongoing 2018
AMG412 ADCC/CDC Disease modifying
SLE phase III no improvement
Eptinezumab FDA review Monoclonal antibody Disease modifying Calcitonin gene-related
ALD403 possible 2019 IgG1k Migraine phase III peptide
Erenumab Aimovig Human monoclonal Disease modifying Calcitonin gene-related
FDA May 2018 antibody IgG2l Migraine phase III peptide (CGRP)
Erlizumab Humanized IgG1 F(ab’)2 Antineoplastic LGL type leukemia ITGB2 (CD18) and LFA-1
Rhumab CD18 fragment (lab tests) block growth factor of
Immunosuppressive drug blood vessels stop
phase I study cough up blood lymphocytes from moving
and phase II did not meet goals into inflamed tissue
Heart attack, stroke, traumatic
shock ??no successful CD18

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

drug to date
Ertumaxomab Rexomun Rat/murine hybrid Antineoplastic Intravenous HER2/neu, CD3
triomab, murine IgG2a Breast
HET2 target, RAT IgG2bl Gastric, esophageal
CD3 target Phase II studies terminated
company to focus on other
plans not safety concerns
concentrate on catumaxomab
Phase I found safe 2016
Etaracizumab or Abegrin Humanized monoclonal Antineoplastic Intravenous Integrin avb3
etaratuzumab Vitaxin antibody IgG2k Melanoma phase II 2010 not
MEDI-522 beneficial, prostate cancer,
ovarian cancer small and large
bowel cancer phase I and II
completed results unreported
2017
Etigilimab Humanized monoclonal Nothing on pubmed or TIGIT T-cell
antibody IgG1k clinical trials immunoreceptor with Ig
Substance is registered and ITIM domains
with FDA, or is not in
creative lab
Etrolizumab Humanized monoclonal Disease modifying Subcutaneous Integrin b7
PRO145223 antibody IgG1k Inflammatory bowel disease Inhibits binding of
RHUMAB UC phase III 2020  4/2023/ aEb7 to E-cadherin
BETA7 2024/2025
Crohn phase III 2021
Evinacumab Human monoclonal Disease modifying Angiopoietin 3
REGN1500 antibody IgG4k Dyslipidemia
Phase II 2020

285
Phase III 2020/2022
Continued
 286
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Evolocumab Repatha Human monoclonal Disease modifying Subcutaneous Proprotein convertase
FDA 2015 antibody IgG2l hypercholesterolemia subtilisin kexin type 9
EU 2015 Completed phase III (PCSK9)
Heterozygous familial
hypercholesterolemia, CVD
Exbivirumab Humanized monoclonal Disease modifying prevent Oral therapy Hepatitis B surface
antibody IgG1l disease Hep B Abstract of randomized antigen
study of 50 patients
Fanolesomab NeutroSpec Murine monoclonal Diagnostic imaging CD15
RB5-IGM antibody Appendicitis (diagnosis only)
Faralimomab Murine monoclonal Nothing on PubMed or Interferon receptor
antibody IgG1 clinical trials
Substance is not
registered with FDA, or is
not in creative lab
Faricimab Humanized monoclonal Disease modifying Intravitreous ANTIVASCULAR
RG7716 antibody IgG1mab angiogenesis, ocular vascular ENDOTHELIAL GROWTH
RO6867461 diseases FACTOR/
STAIRWAY, BOULEVARD, ANTIANGIOPOIETIN 2
RHINE, Yosemite phase II and BISPECIFIC ANTIBODY
III studies phase III 2022 for (VEGF-A and Ang-2)
diabetes maculae edema
AMD LUCERNE phase III 2022
TENAYA phase III 2022
Farletuzumab Humanized monoclonal Antineoplastic Intravenous Folate receptor 1
MORAB-003 antibody IgG1k Ovarian cancer phase III
subgroup may benefit
Fasinumab Human monoclonal Disease modifying acute Subcutaneous (auto Human nerve growth
REGN475 antibody IgG4k sciatic pain phase III injector) factor (HNGF)
SAR164877 Knee arthritis pain phase III
MT5547 2021
FBTA05 Lymphomun Rat IgG2b (CD3)/murine Antineoplastic Intravenous? CD20/CD3
Bi20 IgG2a (CD20) hybrid Chronic lymphocytic leukemia
trifunct trial terminated recruitment too
slow
Felvizumab Humanized monoclonal Antiinfectious agent Nothing on PubMed or Respiratory syncytial virus
antibody IgG1k Respiratory syncytial virus clinical trials
infection Substance is not
registered with FDA, but is
in creative lab
Fezakinumab Human monoclonal Disease modifying Intravenous IL-22
antibody IgG1l Rheumatoid arthritis, psoriasis
(not good for)
Atopic dermatitis phase IIb
good results
Fibatuzumab Humanized monoclonal Disease modifying Ephrin receptor A3

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Ifabotuzumab antibody IgG1k Myelodysplastic syndrome
Research in Australia for GBM
phase I
Ficlatuzumab Humanized monoclonal Antineoplastic Intravenous Hepatocyte growth factor
SCH 900105 antibody IgG1k Head and neck cancer phase I (HGF) hepapoietin A
AV 299 2020
Pancreatic phase I 2023
NSCLC phase I/II 2013
AML phase I 2020
Figitumumab Human monoclonal Antineoplastic Insulin-like growth factor
CP751871 antibody IgG2k Adrenocortical carcinoma, receptor IGF-1 receptor
Ceased development in nonsmall cell lung carcinoma (CD221)
2011 by pfizer etc. ?additional benefit in
phase I
Firivumab Human monoclonal Disease modifying Nothing on PubMed or INFLUENZA A VIRUS
antibody IgG1k Influenza A virus hemagglutinin clinical trials HEMAGGLUTININ HA
Substance is registered
with FDA, and is in
creative lab
Flanvotumab Human monoclonal Antineoplastic Intravenous TYRP1 (glycoprotein 75)
IMC20D7S antibody IgG1k Melanoma phase I 2012 No published data
Fletikumab Human monoclonal Disease modifying IL 20
antibody IgG4 Rheumatoid arthritis
phase IIa good, phase IIb no
results
Flotetuzumab Humanized di-scFv Antineoplastic Intravenous? IL 3 receptor
MGD006 dual affinity retargeting Hematologic malignancies
S80880 (DART) to CD123 and CD3 (ALL, NHL)
Phase II not yet recruiting 2018

287
Continued
TABLE 16.1

288
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Fontolizumab HuZAF Humanized monoclonal Disease modifying IFN-g
antibody IgG Treat Crohn’s clinical
development stopped despite
some benefit phase II
ustekinumab is better
FOR46 Antibody drug conjugate Antineoplastic Intravenous CD46
Phase I for multiple myeloma
failed remission or relapse
Phase I prostate cancer
Foralumab Human monoclonal Disease modifying NASH Oral CD3 epsilon
antibody IgG1k phase II 2019
Foravirumab Human monoclonal Disease modifying rabies Nothing in pub med or Rabies virus glycoprotein
antibody IgG1k (prophylaxis) clinical trials
Fremanezumab Ajovy Humanized monoclonal Disease modifying migraine Subcutaneous a-Calcitonin gene-related
LBR-101 FDA 2018 antibody IgG2k and cluster headache phase III peptide
RN307 2019
Fresolimumab Humanized monoclonal Disease modifying Need larger study for TGF b 1
antibody IgG4 Idiopathic pulmonary fibrosis FSGS
(IPF), scleroderma, focal Good response
segmental glomerulosclerosis scleroderma
(phase 2), cancer (kidney https://
cancer and melanoma) [Link]/
2016/01/30/
fresolimumab/
Frovocimab Humanized monoclonal Disease modifying Subcutaneous PROPROTEIN
LY3015014 antibody IgG4k hypercholesterolemia CONVERTASE
Completed phase II trials 2014 SUBTILISIN KEXIN 9
good response and safe (PCSK9)
Frunevetmab Veterinary monoclonal Veterinary Feline muscle nerve
[Link] antibody IgG1k growth factor
[Link]/
wiki/List_of_
therapeutic_
monoclonal_
antibodies - cite_
note-WHOList
116-17
NV-02
Fulranumab Human monoclonal Disease modifying Subcutaneous Nerve growth factor
AMG403 antibody IgG2k Pain osteoarthritis pain phase
III 2017
Galcanezumab Emgality Humanized monoclonal Disease modifying Subcutaneous Calcitonin gene-related
LY2951742 FDA 2018 antibody IgG4k Migraine polypeptides (CGRPs) a
Phase III completed and b
Cluster HA phase III 2020
Galiximab Chimeric monoclonal Antineoplastic lymphoma Intravenous CD80
IDEC-114 antibody IgG1l phase II 2015 minimal
ADCC/CDC response ORR 10.3%
Gancotamab Human cFv Antineoplastic Intravenous HER2/neu

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

MM-302 Single chain fragment Breast cancer phase IeIII
Ganitumab Human monoclonal Antineoplastic Intravenous IGF-1 receptor (CD221)
AMG479 antibody IgG1k Pancreatic phase IIIdno
increase benefit
Phase III for
rhabdomyosarcoma and
Ewings 2021
Not beneficial in NSCLC
Gantenerumab Human monoclonal Disease modifying Subcutaneous Beta amyloid
R04909832 antibody IgG1k Alzheimers
R1450 Phase III stopped for potential
futility additional studies at
higher dosing (DIAN in a phase
II/III trial in individuals at risk
For and with early-stage
autosomal-dominant AD
phase III 2021
Gatipotuzumab PankoMab-GEX Humanized monoclonal Antineoplastic Intravenous Musculus, antimucin
antibody IgG1k Ovarian, non-small cell lung (MUC1)
cancer (NSCLC), colorectal
cancer (CRC), breast cancer
(BC), gynecological cancers
(GYN) phase I used for diag/
prog now
Gavilimomab Murine monoclonal Disease modifying CD147 (basigin)
ABX-CBL antibody IgM Graft versus host disease
phase III completed 2005 less
effective than antithymocyte
antibody

289
Continued
TABLE 16.1

290
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Gedivumab Human monoclonal Disease modifying No studies Influenza virus
RG7745 antibody IgG1k Influenza virus A PubMed/clinical trials hemagglutinin HA
RO6876802
Gemtuzumab Mylotarg Humanized monoclonal Antineoplastic Intravenous CD33
ozogamicin AML FDA 2000 antibody IgG4/toxin Acute myelogenous leukemia
Voluntary conjugate Many ongoing and completed
withdrawal 2010 studies
VOD now black
box warning
Returned to
market with FDA
approval 2017
Gevokizumab Humanized monoclonal Disease modifying DM phase II Subcutaneous IL-1b
XOMA 052 antibody IgG2k (late stage) no results
Other dz too 24 studies behcet
uveitis failed primary end point
phase III (Eyeguard _B) 2015
Gilvetmab Veterinary monoclonal Antineoplastic No studies clinical trial, CANIS FAMILIARIS
PD1 antibody IgG2k pub med PROGRAMMED CELL
DEATH PROTEIN 1
(PCDC1)
Gimsilumab Human monoclonal Disease modifying Intravenous HUMAN
MORAb-022 antibody IgG1 Rheumatoid arthritis GRANULOCYTE-
Asthma MACROPHAGE
Phase I poster presentation of COLONY-STIMULATING
safety results good 2016 FACTOR (CSF2)
Girentuximab Rencarex Chimeric monoclonal Antineoplastic Intravenous Carbonic anhydrase 9
WX-G250 Reductane antibodyIgG1k Clear cell renal cell carcinoma (CA-IX)
CG250 Radioactive labeled ab for treatment and imaging
Glemba- Human monoclonal Antineoplastic Intravenous Human glycoprotein
tumumab antibody IgG2k Melanoma phase II, breast NMB extracellular
vedotin Antibody drug complex cancer domain (GPNMB)
CR011
Golimumab Simponi Human monoclonal Disease modifying Subcutaneous, TNF-a
CNTO 148 FDA 2009 antibody IgG1k Rheumatoid arthritis, intravenous
EU 2009 psoriatic arthritis, juvenile
rheum arth, ankylosing
spondylitis many studies, UC,
DM1 phase I (2020, 2021)
Gomiliximab Chimeric monoclonal Allergic asthma ? CD23 (IgE receptor)
IDEC-152 antibody IgG1k Antineoplastic CLL
Lumiliximab ADCC/CDC Phase I, phase 2/3 2014
ST-152 Failed efficacy
Gosuranemab FDA orphan drug Humanized monoclonal Progressive supranuclear Intravenous s protein
BIIB092 status antibody IgG4k palsy
IPN-007 Phase I 2020
Alzheimer 2021
Guselkumab Tremfya Human monoclonal Disease modifying Subcutaneous IL23A

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

CNTO 1959 FDA ? antibody IgG1l Psoriasis
Adenomatous polyposis
Hu3F8 Humanized monoclonal Antineoplastic Intravenous GD2 ganglioside
antibody IgG3 Phase I
For neuroblastoma mod tox
and substantial effect on tumor
Phase II ongoing
Ianalumab Human monoclonal Immunomodulation Human cytokine receptor
antibody IgG1k Autoimmune hepatitis BAFF-R
Ibalizumab Trogarzo Humanized monoclonal Disease modifying anti-HIV CD4
FDA/EU antibody IgG4 Phase III
approved
Ibritumomab Zevalin Murine monoclonal Antineoplastic CD20 (human B-
tiuxetan FDA 2002 antibody IgG1k YT77 or Follicular non-Hodgkin’s lymphocyte-restricted
IDEC-129 EU 2004 In98 bound lymphoma, B-cell NHL, differentiation antigen,
IDEC-IN2B8 multiple myeloma conditioning Bp35)
IDEC-Y2B8 for BMT, B-cell DLCL, mantle
cell
Many studies
Icrucumab Human monoclonal Antineoplastic Intravenous Vascular endothelial
IMC 18F1 antibody IgG1k No benefit breast phase II growth factor receptor
No benefit colon phase II (VEGFR-1)
No benefit urothelial phase II
Idarucizumab Praxbind Humanized monoclonal Antidotes Intravenous Dabigatran etexilate
FDA 2015 antibody Fab fragment Drug reversal agent
EU 2015 Reversal of anticoagulant
effects of dabigatran
Phase III trial RE-VERSE AD
Continued

291
 292
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Igovomab Indimacis-125 Murine F(ab’)2 Diagnostic imaging
Ovarian cancer (diagnosis)
Iladatuzumab Humanized monoclonal Antineoplastic Nothing in PubMed or Human gene B29 protein
vedotin antibody IgG1k clinical trials (CD97B)
RG7986
Imalumab Human monoclonal Antineoplastic Intraperitoneal infusion, Macrophage migration
BAX69 antibody IgG1k intravenous inhibitory factor (MIF)
Imaprelimab Humanized IgG1k Antineoplastic Nothing in PubMed or Melanoma cell adhesion
clinical trials molecule (MCAM)
Imciromab Myoscint Murine monoclonal Diagnostic Cardiac myosin
pentetate FDA approved antibody fragment Fab Cardiac imaging
1996 IgG2ak
Withdrawn from
market
Imgatuzumab Humanized monoclonal Antineoplastic Epidermal growth factor
RG7160 antibody IgG1k Colorectal 2013 receptor (EGFR, HER1)
RO5083945 Head and neck 2017
GA201 NSCLC 2017
HUMA-B
IMGN632 Monoclonal antibody with Antineoplastic Intravenous CD123
antibody drug conjugate AML, ALL phase I 2021
NCT03386513
Inclacumab Human monoclonal Disease modifying Intravenous Selectin P
RG1512 antibody IgG4k Cardiovascular disease
RO4905417 phase II
Indatuiximab Chimeric monoclonal Antineoplastic CD138 (syndecan-1)
ravtansine antibody IgG4k Preclinical breast cancer SDC1
Indusatumab Human monoclonal Antineoplastic Intravenous Guanylate cyclase C
vedotin antibody IgG1k Gastrointestinal, pancreatic, (GUCY2C)
TAK-264 conjuagated via a mc-val- gastroesophageal
MLN0264 cit-PABC linker to Safe phase I, phase II
monomethyl auristatin E pancreatic min response, three
{MMAE (5F9-mc-val-cit- studies terminated by
PABC-MMAE)} company business
Inebilizumab Humanized monoclonal Antineoplastic Intravenous CD19
MEDI-551 antibody IgG2k ADCC Refractory DLBCL phase II
2016
Disease modifying systemic
sclerosis, multiple sclerosis
Neuromyelitis optica
Infliximab Remicade Human-murine chimera Disease modifying Intravenous solution TNF-a
FDA 1998 IgG1k Remicade
EU 1999 Human constant, murine Crohn’s disease; ulcerative
Inflectra variable region colitis; rheumatoid arthritis;
FDA 2016 ankylosing spondylitis;

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

EU 2013 psoriatic arthrits; plaque
Remsima psoriasis Inflectra
EU 2013 Spondylitis; ankylosing;
arthritis; rheumatoid colitis;
ulcerative arthritis; psoriatic
Crohn’s disease; psoriasis
Remsima
Spondylitis; ankylosing
arthritis; rheumatoid colitis;
ulcerative Crohn’s disease;
arthritis; psoriatic psoriasis
Inolimomab Murine monoclonal Disease modifying GVHD CD25 (a chain of IL-2
antibody phase III receptor)
No better than ATG in 3 studies
Abandoned not in 2017
Cochrane review
Inotuzumab Besponsa Humanized monoclonal Antineoplastic Intravenous CD22
ozogamicin FDA 2017 antibody IgG4k ADCC/ ALL phase II 2023
G544 CDC Multiple other studies
Intetumumab Human monoclonal Antineoplastic Intravenous CD51
CNTO095 antibody IgG1k Solid tumors (prostate cancer,
melanoma)
Melanoma phase II possible
benefit 2011
Prostate cancer no additional
benefit 2013 phase II
Ipilimumab Yervoy Human monoclonal Antineoplastic agent
FDA 2011 antibody IgG1k Bladder carcinoma (trials
EU 2011 ongoing)
Melanoma

293
Continued
 294
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Ipilimumab Yervoy Human monoclonal Antineoplastic Intravenous CD152 cytotoxic T-
MDX010 FDA 2011 antibody IgG1k Melanoma (checkmate 067) lymphocyte-associated
MDX101 melanoma Renal cell carcinoma antigen 4 (CTLA-4) and
BMS-734016 Metastatic renal (checkmate 214) blocks interaction with its
cancer/ Colorectal cancer ligands CD80/CD86
colorectal Pancreatic?
cancer 2018
Iratumumab Human monoclonal Antineoplastic Hodgkin’s Intravenous CD30 (tumor necrosis
MDX060 antibody IgG1k lymphoma phase II completed factor receptor
Clinical research discontinued superfamily,
2009 Member 8; TNFRSF8) aka
Ki-1 Ag
Isatuximab FDA review Chimeric monoclonal Antineoplastic multiple Intravenous CD 38
SAR650984 possible 2019 antibody IgG1k myeloma
Phase I 2019
Phase II 2022
Phase III 2025
Iscalimab Human monoclonal Disease modifying Intravenous CD40
CFZ533 antibody IgG1k Potential treat autoimmune
disease
Lupus nephritis phase II 2020
Myasthenia gravis
GVHD
Kidney transplant 2022
phase II
Preclinicals
Istiratumab Human monoclonal Antineoplastic Insulin-like growth factor I
MM-005 antibody IgG1 Advanced solid tumors receptor/neuregulin
MM-141 Pancreatic cancer phase II receptor HER3 (IGF1R,
2018 CD221)
Itolizumab Alzumab Humanized monoclonal Disease modifying CD6
FDA antibody IgG1k Psoriasis
GVHS phase II 2022
Ixekizumab Taltz Humanized monoclonal Disease modifying Subcutaneous IL 17A
antibody Phase III radiographic axial
spondyloarthritis
Psoriatic arthritis
Keliximab Chimeric monoclonal Disease modifying CD4
Became antibody IgG1l Chronic asthma
clenoliximab Rheumatoid arthritis
IgG4
Labetuzumab CEA-Cide Humanized monoclonal Antineoplastic Intravenous CEA
hMN14 antibody IgG1 Colorectal cancer
Gastrointestinal phase II
2021imagin
Phase II completed therapy
2003

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Lacnotuzumab Humanized monoclonal Antineoplastic CSF1, MCSF
MCS110 antibody IgG1k Breast, pigmented villonodular
synovitis (PVNS)
Squam ESOP phase II 2024
Gastric 2019
Ladiratuzumab Humanized monoclonal Antineoplastic LIV-1
vedotin antibody IgG1k Phase I triple-negative breast
Antibody drug conjugate cancer 2017 ongoing study
Lampalizumab Humanized monoclonal Disease modifying Intravitreous Complement factor D
RG7417 fragment IgG1k Geographic atrophy (CFD)
secondary to age-related
macular degeneration phase III
Jan 2018 ineffective
Lanadelumab Takhzyro Human monoclonal Disease modifying Subcutaneous Kallikrein (KLKB1)
SHP643 FDA 2018 antibody IgG1k Angioedema phase III 2019
DX-2930
Landogrozumab Humanized monoclonal Disease modifying Intravenous Human growth
LY2495655 antibody IgG4k Muscle wasting disorders, i.e., Subcutaneous differentiating factor 8
after hip surgery phase II (GDF-8) aka myostatin
Pancreatic cancer phase II no (MSTN)
benefit cancer, some muscle
improvement but primary
objective not met
Laprituximab Chimeric monoclonal No trials or PubMed or EGFR
emtansine antibody creative lab only in FDA
IMGN289 registry ?new
Larcaviximab ZMAPP Chimeric monoclonal Disease modifying No studies clinical trial or Ebolavirus glycoprotein
antibody IgG1k Ebola virus PubMed

295
Continued
 296
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Lebrikizumab Humanized monoclonal Disease modifying Subcutaneous injection Interleukin-13 (IL-13)
MILR1444A antibody IgG4k Asthma phase III
TNX-650 Atopic dermatitis HL phase II
RG-3637 2007
PRO301444
Lemalesomab Murine monoclonal Diagnostic agent NCA-90 (granulocyte
antibody IgG1k antigen)
Lendalizumab Humanized monoclonal Disease modifying Intravenous Anticomplement 5A
Olendalizumab antibody IgGk Antiphospholipid syndrome
ALXN-1007 GI GVHD
Lenvervimab Humanized IgG1k Disease modifying No studies in clinical trials Hepatitis B surface
Hepatitis B or PubMed antigen
Lenzilumab Human monoclonal Antineoplastic chronic Intravenous GRANULOCYTEMACRO-
KB-003 antibody myelomonocytic leukemia and PHAGE COLONY-
juvenile myelomonocytic STIMULATING FACTOR
leukemia phase I (GM-CSF)
Lerdelimumab Trabio Human monoclonal Disease modifying Transforming growth
CAT-152 antibody IgG4 Phase I studies factor b 2
?Cancer and fibrosis
Trials stopped for fibrosis after
glaucoma surgery
Leronlimab FDA review 2018 Humanized IgG4k Disease modifying Subcutaneous Chemokine receptor 5
PRO-140 HIV phase III ongoing no (CCR5)
results published good results
phase II
Lesofavumab Human monoclonal Disease modifying No studies clinical trials or Hemagglutinin HA
RG70026 antibody IgG1k Influenza A PubMed
Letolizumab Humanized synthetic light Disease modifying No studies clinical trials or TRAP
chain variable region inflammatory diseases PubMed or creative labs
(scFv)
Lexatumumab Human monoclonal Antineoplastic Intravenous Tumor necrosis factor
HGS1018 antibody IgG1l Breast receptor superfamily
HGS-ETR2 Pancreatic member 10B/death
receptor 5 (TRAIL-R2)
Libivirumab Humanized monoclonal Antiinfectious Oral therapy Hepatitis B surface
antibody IgG1k Prevent disease Hep B Abstract of randomized antigen
study of 50 patients
Lifastuzumab Humanized monoclonal Antineoplastic Intravenous Phosphate-sodium
vedotin antibody Ovarian cancer cotransporter
DBNIB0600A Phase 2
Ligelizumab Humanized monoclonal Disease modifying Subcutaneous Immunoglobulin E (IGHE)
QGE031 antibody IgG1k SSevere asthma and chronic
spontaneous urticaria phase II
and III ongoing trial 2021
Lilotomab Betalutin Murine monoclonal Antineoplastic CD37

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

satetraxetan antibody IgG1 NHL 2020/phase II 2025
Diffuse lg B-cell lymphoma
2019
Lintuzumab Humanized monoclonal Antineoplastic Intravenous CD33
SGN33 antibody IgG1k AMLphase I/II 2022
Mult myeloma phase I 2020
Myelodysplastic phae II 2011
Lirilumab Human monoclonal Antineoplastic Intravenous Killer cell immunoglobulin
IPH2102 antibody IgG4 Solid and hematological like (KIR2D)
cancers Block the interaction
No good aml, squam cell head between KIR2DL-1,-2,-3
neck no good, bladder cancer inhibitory receptors and
ongoing? their ligands
May benefit MDS
Lodelcizumab Humanized monoclonal Disease modifying Unknown studies in Proprotein convertase
LFU720 antibody IgG1k Hypercholesterolemia clinical trials and PubMed subtilisin/kexin type 9
(PCSK9)
Lokivetmab Cytopoint Canis monoclonal Disease modifying Canis lupus familiaris IL31
FDA approved antibody IgG2k Veterinary
for dogs only Clinical signs of atopic
dermatitis in dogs
Loncastuximab Chimeric monoclonal Antineoplastic Intravenous CD19
tesirine antibody IgG1k Diffuse large B-cell lymphoma
ADCT-402 phase II 2020
Lorvotuzumab Humanized monoclonal Antineoplastic Intravenous CD56
mertansine antibody IgG1k SCLC
BB-10901 Ovarian
IMGN901 AML phase II
Wilm, rhabdomyosarcoma,

297
Neuroblast, MPNST, Synovial
sarcoma 2018 phase II
Continued
 298
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Losatuxizumab Chimeric/humanized Antineoplastic Epidermal growth factor
vedotin monoclonal antibody IgG1 (EGRF, ERBB1 HER1)
ABBV-221
Lucatumumab Discontinued Human monoclonal Antineoplastic Intravenous CD40
HCD122 development by antibody IgG1k Multiple myeloma, non-
Novartis 2013 Hodgkin’s lymphoma,
Hodgkin’s lymphoma
Lulizumab pegol Humanized monoclonal Disease modifying Intravenous CD28
antibody SLE Subcutaneous
Phase I safe
Phase II no response
Lumretuzumab Humanized monoclonal Antineoplastic Intravenous CD28; receptor for
RG7116 antibody IgG1k tyrosine-protein
RO5479599 kinase(erbB-3, HER3)
Lupartumab Human monoclonal Antineoplastic Intravenous GPI- anchored cell
amadotin antibody IgG Phase I terminated Why? surface-associated
BAY-1129980 protein C4.4A (LYPD3)
Lutikizumab Humanized monoclonal Disease modifying Subcutaneous Interleukin 1 alpha/
ABT981 antibody Osteoarthritis interleukin 1 beta
Phase IIa no effect
Mapatumumab Human monoclonal Antineoplastic Tumor necrosis factor
HGS1012 antibody IgG4l Hepatocellular no benefit receptor superfamily
Multiple myeloma member 10A; cytokine
Cervical cancer receptor DR4 (death
NSCLC no benefit receptor 4 tumor necrosis
NHL receptor apoptosis-
Bladder cancer may be induced ligand (TRAIL-R1)
beneficial
Margetuximab Chimeric/Humanized Antineoplastic Intravenous erbB2/HER2
MGAH22 monoclonal antibody Breast cancer
IgG1k Gastric cancer/GEC phase Ib/II
trial
Marstacimab Human monoclonal Disease modifying Subcutaneous Tissue pathway factor
PF-06741086 antibody IgG1l Bleeding with hemophilia inhibitor (TFPI)
phase II 2020
Maslimomab Murine monoclonal Immunosuppressive T-cell receptor
antibody Unknown no studies and not
listed in creative lab or FDA
Matuzumab Humanized monoclonal Antineoplastic Intravenous Epidermal growth factor
EMD 72000 antibody IgG1k Colorectal, lung and stomach receptor (EGFR)
cancer weakly beneficial
Mavrilimumab Human monoclonal Disease modifying rheumatoid Subcutaneous GMCSF receptor a-chain
CAM3001 antibody IgG4l arthritis phase IIb good
MEDI565 Fab IgG1 BiTE Antineoplastic Intravenous CD3 and CEA
MT111 Gastrointestinal
AMG211 adenocarcinoma phase I 2018

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Mepolizumab Bosatria Human monoclonal IgG1k Disease modifying Subcutaneous Interleukin-5 (IL-5)
SB-240563 Nucala No benefit in eosinophilic antagonist
FDA 2015 esophagitis
EU 2015 Beneficial allergic severe
asthma
Metelimumab Humanized monoclonal Disease modifying Dropped from further TGF b 1
CAT 192 antibody IgG4 Scleroderma development
Milatuzumab Humanized monoclonal Antineoplastic Intravenous CD74
HLL1 antibody IgG1k Multiple myeloma
IMMU-115 Lupus
Leukemia
Minretumomab Murine monoclonal Diagnostic Tumor-associated
MOAB CC49 antibody IgG1 Tumor detection/diagnostic/ glycoprotein 72 (TAG-72)
prognostic
Failed phase I clinical trials
Mirikizumab Humanized monoclonal Disease modifying Intravenous IL23A
LY3074828 antibody Psoriasis phase III 2020
UC phase III 2023
LUCENT 1 2021 phase III
LUCENT 2 2022
Mirvetuximab Chimeric monoclonal Antineoplastic Intravenous Folate receptor alpha
soravtansine antibody IgG1 Ovarian phase III 2019
M9346A Breast ca phase II 2020
IMGN853
Mitumomab Murine monoclonal Antineoplastic GD3 ganglioside
BEC-2 antibody SCLC phase III no benefit 2005
Modotuximab Chimeric monoclonal Antineoplastic Subcutaneous EGFR extracellular
1024 DS antibody IgG1k Antineoplastic domain III/HER1
Zatuximab Colorectal

299
Futuximab Phase 2019
SYM004 Phase III 2025
Continued
TABLE 16.1

300
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Mogamulizumab Poteligeo Humanized monoclonal Antineoplastic Intravenous CC chemokine receptor
AMG761 FDA 2018 antibody IgG1k Adult T-cell leukemia/ CCR4
KM8761 lymphoma
Solid tumors
Many studies ongoing
MOR202 Human monoclonal Antineoplastic multiple Intravenous CD38
MOR03087 antibody IgG1 myeloma phase I 2018
Monalizumab Humanized monoclonal Disease modifying Intravenous Killer cell lectin-like
NN8765 antibody IgG4k Rheumatoid arthritis, receptor subfamily C
IPH2201 antineoplastic gynecologic member1 (NKG2A,
malignancies, and other CD159A, CD94) that
cancers phase II 2021 recognize nonclassical
NSCLC phase II 2022 HLA (i.e., HLA-E)
s/p stem cell transplant phase I
2020
CLL phase II 2019
Morolimumab Human monoclonal ?Diagnostic No studies in pub med, Rhesus factor
antibody IgG1 creative lab or FDA
substance
Mosunetuzumab Humanized monoclonal Antineoplastic Intravenous CD3E, MS4A1, CD20
RG7828 antibody IgG1k bispecific NHL phase II 2023 Subcutaneous
BTCT4465A DLBCL phase II 2023
Motavizumab Numax Humanized monoclonal Disease modifying Intramuscular Respiratory syncytial virus
MEDI-524 FDA not antibody IgG1k Respiratory syncytial virus glycoprotein F
approved 2010 phase III completed
Older drug just Safety concerns hives and
as effective with allergic reactions
less side effects
Moxetumomab Lumoxiti Recombinant Antineoplastic Intravenous CD22
pasudotox FDA 2018 immunotoxin comprised Hairy cell leukemia
of a variable fragment (Fv) Phase I ALL peds
of a Murine IgG4 anti-
CD22 monoclonal
antibody genetically
Fused to a truncated
fragment of Pseudomonas
exotoxin A
Muromonab- Orthoclone Humanized monoclonal Disease modifying Intravenous CD3
CD3 OKT3 antibody IgG2ak Prevention of kidney transplant Oral
Muromab FDA 1986 rejection
Aka teplizimab/ EU 1986 Many trials GVHD, NASH and
MGA031 (country specific T2DM, giant cell myocarditis
approval) AbATE
Nacolomab Murine monoclonal Antineoplastic No studies in clinical trial C242 antigen
tafenatox fragment Fab ?Colorectal cancer or PubMed
Namilumab Human monoclonal Disease modifying Subcutaneous Colony-stimulating factor
MT203 antibody IgG1k Ank spond psoriasis, RA 2 (CSF2)
phase II

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Naptumomab Murine monoclanl Antineoplastic Intravenous Tumor-associated
estafenatox antibody fragment Fab Nonsmall cell lung carcinoma, antigen 5T4
TTS-CD3 renal cell carcinoma phase III
ANYARA completed primary endpoint
ABR-217620 not achieved
Naratuximab Chimeric monoclonal Antineoplastic Intravenous Tetraspanin-26 (CD37)
emtansine antibody IgG1k B-Cell lymphoma
IMGN529 NHL
Narnatumab Human monoclonal Antineoplastic Intravenous Human cell surface
IMC-RON-8 antibody IgG1k Solid tumors phase I receptor RON (CD 135)
Ron8 macrophage-stimulating
1 receptor
Natalizumab Tysabri Humanized monoclonal Disease modifying Intravenous L selectin (CD62L)
Antegran FDA 2004 antibody IgG4k Relapsing multiple sclerosis, a4-subunit of a4b1 and
Antegren EU 2006 Crohn’s disease a4b7 integrins of
leukocytes (except
neutrophils) (VLA-4)
Navicixizumab Humanized/chimeric Antineoplastic Intravenous Delta-like 4 (DLL4)
OMP 305B83 monoclonal antibody Phase I study colorectal Vascular endothelial
IgG2k gyn tumors growth factor A (VEGF-A)
Navivumab Human monoclonal Disease modifying No studies PubMed Influenza A virus
CT-P27 antibody IgG1k Influenza A hemagglutinin HA
Naxitamab Humanized monoclonal Antineoplastic ?Intravenous c-Met
HU3F8 antibody IgG3 High-risk neuroblastoma and Ganglioside anti-GD2
refractory osteomedullary
disease study 2023
Nebacumab Humanized monoclonal Withdrawn for safety, Endotoxin
antibody IgM Efficacy and commercial

301
reasons
Continued
 302
Immunologic Concepts in Transfusion Medicine
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Necitumumab Portrazza Human monoclonal Antineoplastic Intravenous EGFR
IMC-11F8 FDA 2015 antibody IgG1k Nonsmall cell lung carcinoma
EU 2016
Nemolizumab Humanized monoclonal Disease modifying Subcutaneous Interleukin-31 receptor A
CIM331 antibody IgG2k Eczema phase I and II (IL31RA)
CD14152
NEOD001 Humanized monoclonal Disease modifying Intravenous Amyloid A protein/
Birtamimab antibody IgG1k Primary systemic amyloidosis amyloid light chain
ELT1-01 lack clinical benefit
HU2A4
Nesvacumab Human monoclonal Antineoplastic Intravenous Angiopoietin 2
REGN910 antibody IgG1k Solid tumors not as beneficial
SAR307746 as other agents in breast
cancer
Disease modifying
Macular degeneration
Netakimab Chimeric monoclonal Disease modifying Interleukin 17A
antibody Psoriasis
PLANETA study (Russia, future
EU and China)
Nimotuzumab Theracim Humanized monoclonal Antineoplastic Intravenous EGFR
Theraloc antibodyIgG1k Squamous cell carcinoma,
head and neck cancer,
nasopharyngeal cancer,
glioma
Nirsevimab Human monoclonal Disease modifying Intramuscular Respiratory syncytial virus
MEDI8897 antibody IgG1k Respiratory syncytial virus fusion protein (RSVFR)
phase II 2018
Nivolumab Opdivo Human monoclonal Antineoplastic agent Intravenous Blocks the interaction
FDA 2015 antibody IgG4k Programmed death receptor-1 between PD-1 and its
EU 2015 immunoglobulin (PD-1) blocking antibody ligands, PD-L1 and PD-L2
NSCLC, bladder cancer, renal
cell cancer phase III 2021
Hodgkin lymphoma
Melanoma
Small cell lung cancer
Squamous carcinoma head
and neck
Colorectal cancer
GBM no added benefit 2017

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Nofetumomab Verluma Murine monoclonal Cancer diagnostic imaging Antitumor
merpentan FDA 1996 fragment IgG2bk Fab SCLC Membrane-spanning 4-
No longer domains, subfamily A,
marketed in USA member 1
Obiltoxaximab Anthim Chimeric monoclonal Disease modifying Intravenous Bacillus anthracis spores
ETI-204 FDA 2016 antibody IgG1k Bacillus anthracis anthrax Intramuscular PA component of
phase IV 2021 B. anthracis toxin
Obinutuzumab Gazyvaro Humanized monoclonal Antineoplastic lymphoma Intravenous CD20
GA101HUMAB FDA 2013 antibody IgG1k phase II (MCL, DLBCL) Induces B-cell apoptosis
RG7159 Chronic lymphocytic
RO5072759 leukemia
Afutuzumab Phase II 2021
Ocaratuzumab Humanized monoclonal Antineoplastic Intravenous CD20
LY2469298 antibody IgG1k NHL
AME-133V Pemphigus phase III
Ocrelizumab Ocrevus Humanized monoclonal Disease modifying Intravenous CD20
FDA 2017 antibody IgG1k Multiple sclerosis
Odulimomab Murine monoclonal Disease modifying Lymphocyte function-
antibody Transplant rejection associated antigen-1
Only studied in mice (LFA-1 (CD11a))
Ofatumumab Arzerra Human monoclonal Antineoplastic CLL Intravenous CD20
FDA 2009 antibody IgG1k Phase III 10% ORR after ritux
EU 2010 Complement-dependent Phase II as first line 86% ORR
cytotoxicity (CDC) With CHOP 100% ORR with
62% CR
Olaratumab Lartruvo Human monoclonal Antineoplastic Intravenous Platelet derived growth
IMC3G3 FDA 2016 antibody IgG1k Sarcoma phase II 2023 factor receptor alpha
EU 2016 Ovarian not beneficial (PDGF-R a)

303
Continued
TABLE 16.1

304
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Oleclumab Human monoclonal Antineoplastic pancreatic Intravenous? 50 -nucleotidase
MEDI9447 antibody IgG1l phase II 2021 CD73
Colorectal cancer
Bladder cancer phase I 2020
Breast cancer phase II 2022
NSCLC phase II 2022
Olokizumab Humanized monoclonal Disease modifying rheumatoid IL6
antibody IgG4k arthritis
Phase I 2014 phase IIb mod
results
Omalizumab Xolair Humanized monoclonal Disease modifying allergic Subcutaneous IgE Fc region
IGE25 antibody IgG1k asthma
RG3648 Urticaria
Omburtamab Murine monoclonal Antineoplastic Intracerebroventricular CD276
antibody IgG1k Neuroblastoma treatment
Phase III 2022
OMS721 Human monoclonal Disease modifying Intravenous Mannan-binding lectin-
antibody Atypical hemolytic uremic associated serine
syndrome phase III 2020 protease-2 (MASP-2)
Lupus nephritis phase II 2018
Onartuzumab Humanized monoclonal Antineoplastic Intravenous Human scatter factor
PRO143966 antibody IgG receptor kinase
RO5490258
METMAB
Ontuxizumab Chimeric/humanized Antineoplastic Intravenous Endosialin tumor
MORAB-004 monoclonal antibody No clinical response endothelial marker-1
(TEM1)
Onvatilimab Human monoclonal Nothing in PubMed Vista (V-domain
antibody IgG1k immunoglobulin
suppression of T
activation (VSIR)
Opicinumab Human monoclonal Disease modifying multiple Leucine-rich repeat and
BIIB033 antibody IgG1 sclerosis immunoglobulin domain
Phase II 2020 containing neurite
outgrowth inhibitor
receptor interacting
protein-1 (LINGO-1)
LINGO-1
Oportuzumab Vicinium Humanized monoclonal Antineoplastic Intravescical Epithelial cell adhesion
monatox Proxinium antibody fragment Bladder phase III molecule (EPCAM) and
VB4-845 FDA 2005 scFv Head and neck cancer tumor-associated calcium
EU 2005 signal transducer 1
Additional (TACSTD1) and
approval pseudomonas exotoxin A
pending 2019 immunotoxin fusion
protein (anti-EPCAM
antibody fragment-
Pseudomonas exotoxin
fusion protein)

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Oregovomab OvaRex Murine monoclonal Antineoplastic Subcutaneous CA-125
MAB-B43.13 antibody IgG1k Ovarian cancer Intravenous
Antiidiopathic antibody to Not effective in achieving
ovarian antigen CA-125 increase RFS or OS
Ovarian phase I 2021
Phase II 2019
Orticumab Human monoclonal Disease modifying Oxidized low-density
RG7418 antibody fragment Fab Antiinflammatory lipoprotein oxLDL
Otelixizumab Chimeric humanized Disease modifying Subcutaneous CD3
monoclonal antibody IgG1 Diabetes mellitus type 1
TTEDD phase II
DEFEND-1 phase III failed
DEFEND-2 phase III- no real
benefit
Otilimab Human monoclonal Disease modifying Intravenous Granulocyte-macrophage
MOR103 antibody IgG1l Osteoarthritis, rheumatoid colony-stimulating factor
GSK3196165 arthritis phase II 2012 (GMCSF)
Multiple sclerosis phase II
2014
Otlertuzumab Humanized monoclonal Antineoplastic Intravenous CD37
TRU-016 antibody IgG fragment CLL phase I and II 2014 and
2019
Oxelumab Human monoclonal Disease modifying Intravenous OX-40 (CD252)
OX40L antibody IgG1k Asthma mainly preclinical mice
R4930 Many clinical studies ongoing
HUMAB OX40L leukemia and asthma
Ozanezumab Humanized IgG1 Disease modifying Intravenous Neurite outgrowth
GSK1223249 ALS phase II 2015 ALS no inhibitor (NOGO-A)
good

305
Continued
 306
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Ozoralizumab Humanized monoclonal Disease modifying Subcutaneous TNF-a
ATN 103 antibody Rheumatoid arthritis phase II
2012
Pagibaximab Chimeric monoclonal Disease modifying Intravenous Lipoteichoic acid
antibody Staph sepsis low birth weight
infants
Phase II/III studies 2010
Palivizumab Synagis, Humanized monoclonal Disease modifying Intramuscular F protein of respiratory
Abbosynagis antibody IgG1k RSV many phase III studies syncytial virus
FDA 1998
EU 1999
Pamrevlumab Human monoclonal Disease modifying Connective tissue growth
FG-3019 antibody IgG1k Idiopathic pulmonary fibrosis factor (CTGF)
(IPF), Insulin-like growth factor
Antineoplastic binding protein 8
Pancreatic cancer (IGFBP-8)
Muscular dystrophy phase II
2021
Diabetes nephropathy
Panitumumab Vectibix Human monoclonal Antineoplastic Intravenous EGFR/erbB-1/HER1
ABENIX FDA 2006 antibody IgG2k Metastatic colorectal cancer
ABX-EGFhttps:// EU 2007
[Link].
org/wiki/List_of_
therapeutic_
monoclonal_
antibodies - cite_
note-
WHOList91-38
PankoMab-GEX Humanized monoclonal Antineoplastic Intravenous Tumor-specific
Gatipotuzumab antibody IgG1k Phase IIb 2017 glycosylation of MUC1
Phase I solid tumors 2019
Panobacumab Human monoclonal Antimicrobial Intravenous Pseudomonas aeruginosa
Aerumab 11 antibody Pseudomonas aeruginosa serotype O11
AR-101 infection
KBPA-101
Parsatuzumab Human monoclonal Antineoplastic Epidermal growth factor-
MEGF0444A antibody IgG1k Colorectal cancer phase II like domain 7 (EGFL7)
RG-7414 2014 no benefit
Pascolizumab Humanized monoclonal Disease modifying IL-4
antibody Not effective trails aborted
Pasotuxizumab Chimeric/humanized Antineoplastic No studies Folate hydrolase/
monoclonal antibody prostate-specific
fragment membrane antigen
(PSMA)

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Pateclizumab Humanized monoclonal Disease modifying rheumatoid Subcutaneous Lymphotoxin-a
RG7415 antibody IgG1k arthritis
PRO283698 Phase II not as efficacious as
MLTA3698A adalimumab but had response
Patritumab Human monoclonal Antineoplastic ErbB3 (HER3)
AMG888 antibody IgG1k May not be beneficial head/
U3-1287 neck NSCLC CT site
Spartalizumab FDA review Humanized monoclonal Antineoplastic Intravenous PD1, PDCD1, CD279
PDR001 possible 2019 antibody Breast cancer phase II 2021
NSCLC 2021
Melanoma phase II 2022
Phase III 2020
Pembrolizumab Keytruda Humanized monoclonal Antineoplastic Intravenous PD-1
MK-3475 FDA 2014 antibody IgG4k Squamous carcinoma trachea, Trials for multiple
EU 2015 NSCLC, urothelial (HCC phase myeloma discontinued by
FDA 2018 for II) FDA
metastatic Melanoma
Merkel cell cHL, LgB cell lymph
carcinoma, Gastric cancer
HCC, NSCLC Cervical cancer
Hepatocellular carcinoma
Pemtumomab Theragyn Murine monoclonal Antineoplastic MUC1/human milk fat
HMFG1 antibody antibody Phase III Europe 2009/US globule antigen 1
labeled with 2013 no benefit after 3.5 years (HMFG1)
90Yttrium follow-up
Perakizumab Humanized monoclonal Disease modifying psoriatic IL 17A
antibody IgG1k arthritis
Phase I discontinued
Continued

307
 308
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Pertuzumab Perjeta Humanized monoclonal Antineoplastic agent Intravenous Extracellular dimerization
FDA2012 antibody IgG1 HER2-positive metastatic domain (subdomain II) of
EU 2013 breast cancer the human epidermal
Omnitarg Gastric/breast cancer growth factor receptor 2
Phase III gastric protein (HER2/neu)
Pexelizumab Humanized scFv Disease modifying acute APEX-AMI trial negative C5
myocardial infarctions results
PRIMO-CABG I and II
trials no significant benefit
Pidilizumab Humanized monoclonal Antineoplastic Intravenous PD-1
CT-011 antibody IgG1k Mult myeloma
DLBCL
Pontine glioma
Pancreas
Melenaoma
HCC
Antiinfection
Pinatuzumab Humanized monoclonal Antineoplastic B-cell NHL Intravenous CD22
vedotin antibody phase I study good response
ADC consisting of the Phase II completion 2019
microtubule-disrupting
agent, monomethyl
auristatin E (MMAE),
conjugated to an anti-
CD22 mAbvia the
protease-cleavable
peptide linker
maleimidocaproylvaline-
citrulline(vc)-p-
aminobenzoyloxycarbonyl
Pintumomab Murine monoclonal Not therapeutic Adenocarcinoma
antibody Diagnostic imaging (imaging)
adenocarcinoma antigen
Placulumab Human monoclonal Disease modifying pain and Human TNF
antibody V-kappa)2 FC inflammatory diseases
Development discontinued
2012
Plozalizumab Withdrawn by Humanized monoclonal Disease modifying Intravenous CC chemokine receptor 2
MLN1202 company antibody IgG1k Diabetic nephropathy and (CCR2)
HU1D9 arteriovenous graft patency
RA no benefit
Pogalizumab Humanized monoclonal Antineoplastic Intravenous Tumor necrosis factor
MOXR0916 antibody IgG1k Solid tumors phase I 2019 may receptor superfamily
R07021608 be safe but may not be member 4 (ACT35, OX40,
Vonlerolizumab effective CD134)
No formal manuscripts yet
Polatuzumab FDA review 2018 Humanized monoclonal Antineoplastic Intravenous CD79B

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

vedotin antibody IgG1k NHL phase II 2019
FCU2711 DLBCL phase III 2023
RO5541077-000
Ponezumab Humanized monoclonal Disease modifying Alzheimer’s Intravenous Human beta-40-amyloid
RN1219 antibody IgG2 disease Ab40
PF-04360365 Safe but no clinical efficacy
2013
Porgaviximab Chimeric monoclonal Antiinfectious No known ongoing Zaire ebolavirus
C2G4 IgG1k Ebola virus disease studies glycoprotein
Prasinezumab Humanized monoclonal Disease modifying Intravenous Anti-alpha-synuclein
PRX002 antibody IgG1k Parkinson’s disease (NACP)
RG7935 Phase II 2021
RO7046015
Prezalizumab Humanized monoclonal Disease modifying Subcutaneous B7-related protein
AMG-557 antibody IgG2 SLE phase II 2018 inducible T-cell
MEDI5872 Sjogren’s costimulator ligand
(ICOSL)
Priliximab Chimeric monoclonal Disease modifying IN FDA no known studies CD4
cMT 412 antibody Crohn’s disease, multiple
CEN 000029 sclerosis
Pritoxaximab Chimeric monoclonal Antiinfectious E. coli shiga toxin type-1
antibody IgG1k
Pritumumab Human monoclonal Antineoplastic Vimentin
antibody IgG1k Brain cancer
Phase II studies in Japan,
could not find literature
reportedly increase
survivability 10 fold

309
Continued
 310
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Quilizumab Humanized monoclonal Disease modifying Subcutaneous M1 prime segment of
MEMP1972A antibody IgG1k Asthma phase II 2014 no great Intravenous membrane bound IgE
RG-7449 benefit (IGHE)
Anti-M1 Urticaria phase II 2014 no great
benefit
Allergic rhinitis
Racotumomab Vaxira Murine monoclonal Antineoplastic Intradermal N-glycolylneuraminic acid
antibody IgG1k Nonsmall cell lung cancer Subcutaneous gangliosides (NGNA
phase III 2016 cimavax better ganglioside)
(recombinant EGF injection) 2
more months survival over
placebo
Neuroblastoma phase II 2020
Radretumab Human monoclonal Antineoplastic Fibronectin extra
F16SIP antibody Lymphoma brain mets 2012 domain-B
L19SIP Imaging study PET phae I
radiolabeled with Stage III NSclC
I331
Rafivirumab Human monoclonal Antiinfectious No known studies Rabies virus glycoprotein
CR57 antibody IgG1l Rabies (prophylaxis)
Used in cocktail and with
vaccination
Ralpancizumab Humanized monoclonal Disease modifying PCSK9 (proprotein
RN317 antibody IgG2k Dyslipidemia phase I 2017 convertase subtilisin/
PF-05335810 kexin type 9, neural
apoptosis-regulated
convertase 1, NARC1,
NARC-1, proprotein
convertase 9, PC9)
Ramucirumab Cyramza Human monoclonal Antineoplastic Intravenous VEGFR2
LY3009806 FDA 2014 antibody IgG1k Urothelial phase III done
IMC-1121B EU 2014 Adenocarcinoma stomach
and GE junction phase II 2023
Colorectal cancer
NSCLC
HCC phase III 2017 no
additional benefit
Ranevetmab Veterinary monoclonal Disease modifying Nerve growth factor-b
NV-01 antibody IgG1k canine Osteoarthritis in dogs (NGF-b)
Ranibizumab Lucentis Humanized monoclonal Disease modifying Intravitreal Vascular endothelial
RBZ FDA 2006 fragment IgG1k Fab Macular degeneration (wet growth factor A (VEGF-A)
RG-3645 EU 2007 form) post market studies
RHuFAb phase II
Ravagalimab Humanized monoclonal Disease modifying UC phase II Intravenous CD40
PR-1629977 antibody IgG1k 2023 Subcutaneous
ABBV-323

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Ravulizumab Ultomiris Humanized monoclonal Disease modifying Intravenous Complement C5 (C5)
ALXN1210 FDA 2019 antibody IgG2/IgG4k Paroxysmal nocturnal
EU pending hemoglobinuria (PNH)
Phase III 2021 similar to
eculizumab, atypical hemolytic
uremic syndrome phase III
2021
Raxibacumab ABthrax Human monoclonal Antiinfectious Intravenous Bacillus anthracis
FDA 2012 antibody IgG1l Treat inhalation anthrax protective antigen
Refanezumab Humanized monoclonal Disease modifying recovery of Intravenous Myelin-associated
GSK249320 antibody IgG1k motor function after stroke glycoprotein
Phase II completed 2011 no
benefit
Regavirumab Human monoclonal Antiinfectious Cytomegalovirus infection
MCA C23 antibody Cytomegalovirus
TI-23 glycoprotein B
ONLY STUDIES IN RATS 1994
Relatlimab Human monoclonal Antineoplastic Intravenous Lymphocyte activation
BMS-986016 antibody IgG4k Melanoma phase II 2022 gene 3 (LAG3) CD223
Colon cancer phase II 2022
Chordoma phase II 2020
Cannot find manuscripts but
company website phase II
good results
Glioblastoma phase I 2020
Remtolumab Human monoclonal Disease modifying Subcutaneous Interleukin 17 alpha,
ABT-122 antibody RA TNF-a
Phase II 2016 no increased
benefit over adalimumab

311
Continued
 312
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Reslizumab Cinqair Humanized monoclonal Disease modifying Intravenous IL-5
DCP 835 FDA 2016 antibody IgG4k Inflammations of the airways Subcutaneous
Scheme 55700 EU 2016 asthma completed and
CEP-38072 ongoing, skin and
gastrointestinal tract,
polyarteritis stage II 2018
Rhino sinusitis 2020
Rilotumumab Human monoclonal Antineoplastic Intravenous Hepatocyte growth factor
AMG-102 antibody IgG2k Gastric completed phase III (HGF)
2015 not effective
NSCLC phase II 2014 no
benefit
Glioma phase II no response
Rinucumab Human monoclonal Disease modifying Intravitreal Platelet-derived growth
REGN2176 antibody IgG4k neovascular age-related factor receptor beta
macular degeneration phase II
2014
Risankizumab FDA/EU pending Humanized monoclonal Disease modifying Crohn’s Subcutaneous IL23A
ABBV-066 approval antibody IgG1k disease phase II good, phase
BI-655066 III ongoing
psoriasis phase II response
better than ustekinumab,
psoriatic arthritis, and asthma
Rituximab MabThera, Chimeric monoclonal Antineoplastic Subcutaneous CD20
GP2013 Rituxan antibody IgG1k Non-Hodgkin lymphomas,
IDEC-102 FDA 1997 chronic lymphocytic
RG-105 EU 1998 leukemias, some autoimmune
disorders, i.e., rheumatoid
arthritis, >2K studies ongoing
Rivabazumab Humanized monoclonal Antiinfectious No studies found Pseudomonas aeruginosa
pegol antibody fragment Fab’ type III secretion system
IgG1k
Rmab Rabishield Human monoclonal Antiinfectious Rabies virus G
Made in India antibody Postexposure prophylaxis of glycoprotein
rabies
Robatumumab Human monoclonal Antineoplastic Intravenous Insulin-like growth factor I
19D12 antibody IgG1k Colorectal phase II 2009 little (IGF-1 receptor) (CD221)
SCH 717454 benefit
MK-7454 Ewings no response 2016
P04722
Roledumab Human monoclonal Immunomodulation Intravenous RHD
antibody IgG1k Rh disease
Phase III 2017
Romilkimab Humanized chimeric Disease modifying Subcutaneous Interleukin 13 and IL4
SAR156597 monoclonal antibody IgG4 Systemic sclerosis phase II

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

HUBTI3_2_1 bispecific 2019
Pulm fibrosis phase II 2017 no
benefit
Romosozumab Evenity Humanized monoclonal Disease modifying Intravenous Sclerostin/scleroscin
FDA pending antibody IgG2k Postmenopausal osteoporosis SOST
EU pending phase III study FRAME
Japan 2018 Men phase III
BRIDGE phase III
Rontalizumab Humanized monoclonal Disease modifying Subcutaneous IFN-a
rhuMAb antibody Systemic lupus erythematosus
IFNalpha phase II 2013 end points not
met
Rosman- Humanized monoclonal Antineoplastic Intravenous Root plate-specific
tuzumab antibody IgG1k Colorectal cancer phase I 2018 spondin r-spondin-3
OMP-131R10 WNT? (wingless/
integrated)
Rovalpituzumab Humanized monoclonal Antineoplastic Intravenous Delta-like ligand-3 (DLL3)
tesirine antibody IgG1k Small cell lung cancer phase I
SC0002 2018
SC16LD6.5 Phase II 2024
ABBV-181
Rovelizumab LeukArrest Humanized monoclonal Disease modifying CD11, CD18
Hu23F2G antibody IgG1k Hemorrhagic shock, MI stroke
phase III goals not met 2000
Rozano- Chimeric/humanized Thrombocytopenia ITP phase Subcutaneous Neonatal Fc receptor
lixizumab monoclonal antibody II 2019 Intravenous (FCGRT)
UCB7665 IgG4k Myasthenia gravis phase II
2018

313
Continued
 314
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Ruplizumab Antova Humanized monoclonal Disease modifying lupus and BioDrugs. 2004; 18(2): CD154 (CD40L)
antibody lupus nephritis not effective 95e102.
Life-threatening Costimulation blockade in
thromboembolism the treatment of
rheumatic diseases
Sacituzumab FDA/EU pending Humanized monoclonal Antineoplastic agent Intravenous Tumor-associated
govitecan approval antibody IgG1k Prostate cancer phase II 2021 calcium signal transducer
IMMU-132 Urothelial phase II 2020 2 (TROP-2) inhibits
Trip neg breast ca phase III topoisomerase I
2020 NSCLC SCLC UC
Samalizumab Humanized monoclonal Antineoplastic Intravenous OX-2 membrane
ALXN6000 antibody IgG2/G4k CLL MM phase I 2010 glycoprotein (CD200)
BAML-16-001- (terminated by sponsor)
S1 AML phase II 2021
Samrotamab Chimeric/humanized Antineoplastic No studies found Leucine-rich repeat-
vedotin monoclonal antibody containing protein 15
IgG1k (LRRC15)
Sarilumab Kevzara Human monoclonal Disease modifying rheumatoid Subcutaneous IL6
REGN88 FDA?EU/Japan antibody IgG1k arthritis phase III 2015/2020/
SAR153191 under review 2027(preg exposure),
approved in ankylosing spondylitis
Canada Juvenile idiopathic arthritis
phase II 2022
Satralizumab FDA review Humanized monoclonal Disease modifying Subcutaneous? IL6 receptor
SA237 possible 2019 antibody IgG2k Neuromyelitis optica phase III
Sapelizumab 2019/2020
Satumomab OncoScint Murine monoclonal Diagnostic imaging Intravenous Tumor-associated
pendetide CR103 antibody IgGk fragment Detection colorectal and glycoprotein (TAG-72)
FDA 1992 Fab’ ovarian cancer
Secukinumab Cosentyx Human monoclonal Disease modifying Subcutaneous IL 17A
AIN457 FDA 2015 antibody IgG1k Uveitis, rheumatoid arthritis
EU 2015 psoriasis phase II 2019 over
100 other studies arthritis;
psoriatic psoriasis;
spondylitis; ankylosing
Selicrelumab Human monoclonal Antineoplastic Subcutaneous Tumor necrosis factor
CP 870.893 antibody IgG2k Solid tumors phase I 2020 Intravenous receptor superfamily
RG7876 Pancreatic cancer phase II member 5 (CD40)
RO-7009789 2020
Colon cancer phase II 2021
Mesothelioma phase ib 2015
Seribantumab Human monoclonal Antineoplastic Intravenous Receptor tyrosine-protein
MM121 antibody IgG2l Breast phase II 2020 kinase erbB-3 (HER3)
SAR256212 Ovarian phase I 2014
Setoxaximab Chimeric monoclonal Antiinfection No known studies or E. coli shiga toxin type-2
antibody IgG1k E. coli clinical use

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Setrusumab Human monoclonal Disease modifying Intravenous Sclerostin (SOST)
BPS804 antibody IgG2 Osteogenesis imperfecta
MOR05813 phase II 2020
Sevirumab Antiinfectious Cytomegalovirus infection
MSL-109 CMV retinitis early termination
trial secondary to safety
Phase II 2003
SHP647 Human Disease modifying Subcutaneous Mucosal addressin cell
Ontamalimab monoclonalantibodyIgG2k Crohn’s/UC phase III adhesion molecule
PF-00547659 2020e2025  7 (MADCAM)
Phase II study 2007 better
response in UC than in Crohn
(?more time needed to
evaluate clinical significance
Sibrotuzumab Humanized monoclonal Antineoplastic Intravenous FAP
BIBH1 antibody IgG1k Colorectal cancer phase II
F19 2003 failed
Lung cancer2001
Sifalimumab Humanized monoclonal Disease modifying Intravenous IFN-a
MDX-1103 antibody IgG1k SLE phase II 2015 Subcutaneous
MEDI-545 dermatomyositis, polymyositis
CP145
Siltuximab Sylvant Chimeric monoclonal Antineoplastic Intravenous IL-6
CLLB8 FDA 2014 antibody IgG1k Multiple myeloma phase II
CNTO-328 EU 2014 2019
DM type I phase I 2017
Schizophrenia adjunct 2020
phase II
Multicentric Castleman’s

315
disease (MCD) with HIV
negative and HHV-8 negative
Continued
TABLE 16.1

316
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Simtuzumab Humanized monoclonal Disease modifying Subcutaneous Lysyl oxidase homolog 2
AB0024 antibody IgG4k Hepatic fibrosis Intravenous (LOXL2)
GS-6624 Phase II 2016 no benefit
Pulm fibroses phase II 2017 no
benefit
Myelo fibr 2017 phase II
Siplizumab Humanized monoclonal Antineoplastic CD2
MEDI-507 antibody IgG1k T Or NK cells
Sirtratumab Human monoclonal Antineoplastic Nothing in PubMed or SLITRK6
vedotin antibody clinical trials
Sirukumab Human monoclonal Disease modifying Subcutaneous IL-6
antibody IgG1k Rheumatoid arthritis
Phase III done good results
Sofituzumab Humanized monoclonal Antineoplastic CA-125
vedotin antibody Ovarian pancreatic
Phase I (2014)
Solanezumab Humanized monoclonal Disease modifying Alzheimer’s Intravenous Beta amyloid
LY2062430 antibody IgG1 Phase III study discontinued
no effect
In preclinical trial for secondary
prevention 2022
Hereditary AD phase III 2021
Solitomab Murine monoclonal Antineoplastic Intravenous Epithelial cell adhesion
MT110-011 antibody bispecific T-cell Gastrointestinal, lung, and molecule (EpCAM) CD3
AMG110 engager (BiTE) other cancers
Phase I 2015
Sonepcizumab iSONEP Humanized monoclonal Disease modifying Intravenous Sphingosine-1-
LT1009 antibody Choroidal and retinal Intravitreous phosphate (S1P)
neovascularization phase II
2015 not so good
Antineoplastic phase II renal
cancer 2017 potential
Stamulumab Humanized monoclonal Disease modifying muscular Intravenous Myostatin
antibody dystrophy
Animal studies, minimal
efficacy
Phase I/II studies ongoing (no
improvement)
Sulesomab LeukoScan Murine monoclonal IgG1 Diagnostic NCA-90 (granulocyte
IMMU-MN3 EU 1997 fragment Fab0 Osteomyelitis (imaging) antigen)
Suptavumab Human monoclonal Antiinfectious Intramuscular Resp sync virus fusion
REGN2222 antibody IgG1k Medically attended lower protein (RSVFR)
SAR438584 respiratory disease phase III
2017 not meet primary
endpoint
Another study no data yet at
30 mg/kg dose
Sutimlimab Chimeric/humanized Disease modifying cold Intravenous Complement C1s (C1s)
BIVV009 monoclonal antibody agglutinin disease phase III
IgG4k 2020

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Suvizumab Humanized monoclonal Antiinfectious Intravenous Human
KD-247 antibody IgG1k HIV immunodeficiency virus
Phase I KD-247 glycoprotein 120 third
2007 variable loop
Suvratoxumab Human monoclonal Disease modifying Intravenous Staphylococcus aureus
MEDI4893 antibody IgG1k Nosocomial pneumonia phase alpha toxin
II 2018
Tabalumab Human monoclonal Antineoplastic Subcutaneous Cytokine B-cell activating
LY2127399 lantibodyIgG4k Rheum arthr phase III 2013 no factor (BAFF)
signif response
SLE phase III 2015 endpoints
not met
Mult myelo phase I 2014 may
not treat but be prognostic
Tacatuzumab AFP-Cide Humanized monoclonal Antineoplastic No studies in clinical trial Alpha-fetoprotein
tetraxetan antibody yttrium77 or PubMed
HAFP-31
Tadocizumab Humanized monoclonal Disease modifying Integrin aIIbb3
C4G1 antibody fragment IgG1k Percutaneous coronary
YM337 Fab’ intervention phase I 1999
?not further developed
Talacotuzumab Humanized monoclonal Antineoplastic Intravenous Interleukin 3 receptor
CSL362 antibody IgG1-2k AML phase III 2018 subunit-a (IL3Ra, CD123)
JNJ-56022473 MDS phase II 2019
SLE 2019 phase I
Talizumab Humanized monoclonal Disease modifying Subcutaneous IgE
C21/AL-90 antibody IgG1k Peanut allergy
TNX-901 Allergic reaction

317
Phase II 2003 good results
legal issues shelved the drug
Continued
TABLE 16.1

318
Summary of Monoclonal Antibody [Link]'d
Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target

Immunologic Concepts in Transfusion Medicine

Tamtuvetmab Tactress Canine monoclonal CD52
AT-005 antibody IgG2l
Tanezumab FDA review Humanized monoclonal Disease modifying Nerve growth factor (NGF)
RN624 possible 2019 antibody IgG2 Pain
PF-4383119 Osteoarthritis
Back pain
Metastatic cancer pain
Phase II w2008
Tanibirumab Human monoclonal Disease modifying Intravenous VEFR-2
Olinvacimab antibody IgG1 Antineoplastic
TTAC-0001 Phase I glioblastoma 2020
Breast cancer phase I 2020
AMD murine no human studies
found
Taplitumomab Murine monoclonal Antineoplastic No studies pub med or CD19
paptox antibody IgG1k clinical trials
Tarextumab Human monoclonal Antineoplastic Intravenous Notch2/3, Notch receptor
OMP-59R5 antibody IgG2 Phase II trial NSCLC no benefit
2017
Pancreatic phase II 2017
Tavolimab Chimeric/humanized Antineoplastic Tumor necrosis factor
MEDI0562 monoclonal antibody Head and neck phase I 2024 receptor superfamily
IgG1k Ovarian cancer phase II 2023 member 4 (TNFRS4)
OX40L receptor (CD134)
Technetium Rabbit monoclonal IgG Not for use in humans- CEA
(99 mTc) research purpose only
acritumomab
Technicium NeutroSpec Murine monoclonal IgM Disease modifying Intravenous CD15
(99 mTc) FDA2004 radiolabeled osteomyelitis
Fanolesomab Sales and marketing
suspended (2005)
Diagnostic scans for acute
appendicitis
Tefibazumab Aurexis Humanized monoclonal Antiinfectious Intravenous Clumping factor A
INHeH2002 antibody IgG1k Staphylococcus aureus
infection
Phase II 2006
Telimomab Recombinant murine Antineoplastic No studies in pub med or CD5
aritox monoclonal antibody Fab T Cell lymphoma/leukemia clinical trials
(TAB-885) with ricin
Telisotuzumab Humanized monoclonal Antineoplastic Intravenous Hepatocyte growth factor
vedotin antibody IgG1k Phase I 2017 receptor HGFR
ABT-700 SCLC phase II 2022
NSCLC phase II 2021
Tenatumomab Murine monoclonal Antineoplastic Intravenous P24821, tenascin C
antibody IgG2b Phase I 2017
Phase II brain tumors 2010

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Teneliximab Chimeric monoclonal Not in clinical trials 2009 CD40 (TNF receptor
antibody IgG1 superfamily member 5)
Teplizumab Humanized monoclonal Disease modifying type I DM Intravenous CD3
MGA031 antibody IgG1k phase II completion AbATE Subcutaneous
PRV-031 trial 2019
hOKT3g1(Ala- Psoriasis phase I and II
Ala) completed 2010 study
stopped secondary to injection
reaction severe allergy
Tepoditamab Human monoclonal Antineoplastic No studies on PubMed or c-type dendritic cell-
antibody IgG1k bispecific clinical trials associated lectin 2
(CLEC-2A, MCLA-117)
and CD3
Teprotumumab FDA review Human monoclonal Disease modifying Intravenous Insulin-like growth factor
RV001 possible 2019 antibody Thyroid eye disease phase II receptor type I (IGF-1
R-1507 2017 receptor) (CD221)
RO4858696 Graves phase III 2020
HZN-001
Tesidolumab Human monoclonal Phase I 2017 Intravenous C5
LFG316 antibody PNH phase II 2020 Intravitreous
NOV-4 AMD phase II 2015 not
beneficial
Tetulomab Betalutin Humanized monoclonal Antineoplastic CD37
tetraxetan LU- antibody Animal studies 2013
177
Tezepelumab Human monoclonal Disease modifying Subcutaneous Thymic stromal
MEDI9929 antibody IgG2l Asthma, atopic dermatitis lymphopoietin (TSLP)
AMG-157 Phase II 2017

319
Continued
 320
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Theralizumab Humanized monoclonal Antineoplastic Intravenous CD28
TGN1412 antibody Solid tumors phase I 2020 History of cytokine storm
TAB08 Disease modifying at higher doses 2006
Rheum arth, SLE phase II
Tibulizumab Humanized monoclonal Disease modifying Subcutaneous Human B-cell activating
LY3090106 antibody bispecific Autoimmune disorder Intravenous factor of the tumor
tetravalent Phase I 2020 No manuscripts found necrosis factor family
specific to this antibody interleukin 17 (BAFF)
Tigatuzumab Humanized monoclonal Antineoplastic Cytokine receptor DR5
CS-1008 antibody IgG1k Colon phase II 2011no added (death receptor 5)
TRA-8 benefit TRAIL-R2
Colon phase I 2013
NSCLC phase II 2011 no
benefit
Pancreatic phase II 2008
benefit
TN breast canc 2015 phase II
no added benefit
Tildrakizumab Ilumya Humanized monoclonal Immunologically mediated Subcutaneous IL23
MK-3222 Ilumetri antibody IgG1k inflammatory disorders
SCH-900222 FDA 2018 Mod/severe psoriasis phase III
2018-20
Timigutuzumab Humanized monoclonal Antineoplastic No studies in clinical trial erbB2/HER2
antibody IgG1k or PubMed
Timolumab Human monoclonal Disease modifying Intravenous AOC3
BTT-1023 antibody Scler cholang phase II 2019
Tiragotumab Human monoclonal Antineoplastic Intravenous T-cell IG and immune-
MTIG-7192A antibody IgG1k Phase I 2020 Nothing published yet receptor tyrosine-based
RG6058 NSCLC phase II 2021 inhibitory motif (TIGIT)
RO7092284 HL phase II 2019
Tislelizumab China pending Humanized monoclonal Antineoplastic Intravenous PCDC1, CD279
approval antibody NSCLC phase III 2020 Nothing published yet
Gastric phase III 2022 2019
Esophageal cancer phase III
2021
NHL phase II 2020
Tisotumab Human monoclonal Antineoplastic Intravenous Coagulation factor III
vedotin antibody IgG1k Ovary cancer
Cervix cancer
Endometrium cancer
Bladder cancer
Prostate cancer
Esophagus cancer
Lung cancer, NSCLC
Squamous cell carcinoma of

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

the head and neck
Pancreatic phase II 2022/3
Tocilizumab Actemra, Humanized monoclonal Disease modifying Intravenous IL-6 receptor
MRA RoActemra antibody IgG1k rheumatoid arthritis Subcutaneous
R-1569 FDA 2010 >100 studies
RG-1569 EU 2009 Behcet syndrome
RHPM-1
RO-4877533
Atlizumab
Tomuzotuxi- Humanized monoclonal Antineoplastic EGFR, HER1
mabfibri antibody IgG1k Phase I 2019
Toralizumab Humanized monoclonal Disease modifying rheumatoid CD154 (CD40L)
E6040 antibody IgG1k arthritis, lupus nephritis etc.
IDEC-131 Phase II trials failed with TE
Tosatoxumab Human monoclonal Antiinfectious No studies PubMed or Staphylococcus aureus
antibody IgG1l Clin trials a-hemolysin
Tositumomab Bexxar Murine monoclonal Antineoplastic Intravenous CD20
and iodine 131 FDA 2003 antibody IgG2al Follicular lymphoma (NHL)
Tositumomab >100 studies
Tovetumab Human monoclonal Antineoplastic Intravenous Platelet-derived growth
MEDI-575 antibody IgG2k Phase I/II 2012 factor receptor a
Glioblastoma limited clin (CD140a)
activity
Tralokinumab Human monoclonal Disease modifying asthma Intravenous IL-13
CAT-354 antibody IgG4 phase IIb þ/, atopic Subcutaneous
dermatitis phase II 2016
Continued

321
 322
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Trastuzumab Herceptin Humanized monoclonal Antineoplastic Subcutaneous HER2/neu
4D5v8 FDA 1998 antibody IgG1k Breast cancer Intravenous
R-597 EU 2000 Gastric and gastro-
SYD977 Herceptin esophageal junction cancer
Hylecta FDA HER2-positive phase III
2019 e
trastuzumab/
hyaluronidase
Herzuma 2018
Trastuzumab Hercion Antibody drug conjugate Antineoplastic breast cancer HER2
Deruxtecan DS- FDA humanized antibody phase I study breast, gastric,
8201 breakthrough IgG1k with topoisomerase colorectal, salivary, and
therapy I inhibitor (DXd) nonsmall cell lung cancer
participated in part 2 2020
phase II DESTINY-Breast01
Trastuzumab Kadcyla Humanized monoclonal Antineoplastic Intravenous HER2/neu
emtansine FDA2013 antibody IgG1k as ADC Breast cancer
RG-3502 EU 2013
PRO132365
TRBS07 Ektomab 3funct Antineoplastic GD2 ganglioside Tribbles-related protein
Melanoma (TRB) family members are
the mammalian orthologs
of Drosophila tribbles.
Tribbles was originally
identified as a cell cycle
regulator during
Drosophila development.
Tribbles genes are
evolutionary conserved,
and three TRB genes
(TRB1, TRB2 and TRB3)
have been identified in
mammals. TRBs are
considered
pseudokinases because
they lack an ATP binding
site or one of the
 conserved catalytic motifs
essential for kinase
activity. Instead, TRBs
play important roles in
various cellular processes
as scaffolds or adaptors
to promote the
degradation of target
proteins and to regulate
several key signaling
pathways. Recent
research has focused on

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

the role of TRBs in
tumorigenesis and
neoplastic progression. In
this review, we focus on
the physiological roles of
TRB family members in
tumorigenesis through
the regulation of the
ubiquitin-proteasome
system and discuss TRBs
as biomarkers or potential
therapeutic targets in
cancer
Tregalizumab Humanized monoclonal Disease modifying Subcutaneous CD4
BT-061 antibody IgG1k Rheumatoid arthritis
Phase IIb no benefit
Tremelimumab *CP-675,206 Human monoclonal Antineoplastic agent CTLA4 (cytotoxic T
(aka ticilimumab) antibody IgG2 NSCLC, small cell lung cancer, lymphocyte-associated
urethelial cancer phase II 2020, antigen 4, CD152
head and neck cancer and
colon phase I 2021
Mesothelial phase IIb
DETERMINE not beneficial
>100 studies
Trevogrumab Human monoclonal Disease modifying Myostatin, growth
REGN1033 antibody IgG4k Muscle atrophy due to differentiation factor 8
SAR391786 orthopedic disuse and (GDF8)
sarcopenia phase II 2020
TRL3d3 IgG Studies only in mice to this Ati-G protein antibody

323
3D3 point (RSVGV)
Continued
 324
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d
Generic Drug

Immunologic Concepts in Transfusion Medicine

Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Tucotuzumab Humanized monoclonal Antineoplastic Intravenous Interleukin2 (EpCAM)
celmoleukin antibody IgG1 Ovarian phase II 2008
EMD-273066 Lung, kidney, bladder phase I
HUKS-IL2 2000 no benefit
Tuvirumab Humanized monoclonal Antiinfectious Intravenous Hepatitis B virus surface
antibody Not effective in achieving antigen
primary efficacy as assessed
by neutralization of circulating
HBsAg
Ublituximab FDA review Chimeric monoclonal Antineoplastic Intravenous CD20 MS4A1
TG-1101 pending 2019 antibodyIgG1k Chronic lymphocytic leukemia,
follicular cell lymphoma phase
II 2020
Disease modifying
Multiple sclerosis phase II
2019, phase III 2021
Awaiting result looks good
prelim
Ulocuplumab Human monoclonal Antineoplastic CLL phase I Intravenous CXCR4 (CD184)
antibody IgG4 2014
Phase I/II Waldenstrom
macroglobulinemia 2025
Phase I/II AML 2021
Urelumab Human monoclonal Antineoplastic Intravenous Human receptor 4-1BB
BMS-663513 antibody IgG4k CLL phase II 2020 (CD137)
Solid tumors phase II 2023
Urtoxazumab Humanized monoclonal Disease modifying EHEC Escherichia coli (EHEC)
TMA-15 antibody IgG1k animal studies shiga toxin 2
Ustekinumab Stelara Human monoclonal Disease modifying Subcutaneous p40 subunit of interleukin
FDA 2009 antibody IgG1k Crohn disease Intravenous 12 (IL-12p40), IL-23
EU 2009 Plaque psoriasis
Psoriatic arthritis
Utomilumab Human monoclonal Antineoplastic Intravenous 4-1BB (CD137)
PF-05082566 antibody IgG2 Diffuse large B-cell lymphoma
Phase I 2021 phase II 2020
Breast phase II 2025
Vadastuximab Chimeric monoclonal Antineoplastic Intravenous CD33
talirine antibody IgG1k Acute myeloid leukemia phase
H2H12EC II 2017 phase III 2017
MDS phase II 2017
Vanalimab Humanized monoclonal Antineoplastic? No studies clinical trial or Immune checkpoint
Mitazalimab antibody IgG1l PubMed receptor, tumor necrosis
receptor family CD40,
(TNFRSF5)
Vandortuzumab Humanized monoclonal Antineoplastic STEAP1
vedotin antibody Prostate cancer

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

Vantictumab Human monoclonal Antineoplastic Intravenous Frizzled receptor
OMP-18R5 antibody IgG2mab NSCLC, breast phase I 2017
Vanucizumab Humanized monoclonal Antineoplastic Intravenous Angiopoietin 2/vascular
RG-7221 antibody IgG1k bispecific Phase I 2018 endothelial growth
RO5520985 ANG-2/VEGF-Amab factor A
Vapaliximab Chimeric monoclonal No studies in PubMed or Vascular adhesion protein
BTT-1002 antibody IgG2k clinical trials AOC3 (VAP-1)
HUVAP
Varisacumab Human monoclonal No studies in PubMed or VEGF-A
GNR-011 antibody IgG1k clinical trials
R-84
Varlilumab Human monoclonal Antineoplastic Intravenous CD27
CDX-1127 antibody IgG1k Solid tumors and hematologic
malignancies
Phase I 2017, phase II 2019/20
Melanoma phase II 2018/21
Vatelizumab Humanized monoclonal Disease modifying A2b1 integrin I domain
GBR500 antibody IgG4 UC phase II 2016 ITGA2 (CD49b)
SAR339658 MS phase II 2016 withdrawn
lack of efficacy
Vedolizumab Entyvio Humanized monoclonal Disease modifying Intravenous Integrin a4b7
LDP02 FDA 2014 antibody IgG1k Crohn disease Selectively blocks
MLN02 EU 2014 Ulcerative colitis trafficking of
In CD resolution extraintestinal Memory T cells to
manifestations inflamed gut tissue by
inhibiting a4b7-mucosal
addressin cell adhesion
molecule-1 (MAd-CAM-1)
interaction

325
Continued
 326
TABLE 16.1
Summary of Monoclonal Antibody [Link]'d

Immunologic Concepts in Transfusion Medicine

Generic Drug
Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target
Veltuzumab Humanized monoclonal Antineoplastic Subcutaneous CD20
IMMU-106 antibody IgG1k Non-Hodgkin’s lymphoma
HA20 phase II 2013
ITP phase II 2016
Vepalimomab Murine monoclonal AOC3 (vascular adhesion
antibody protein-1)
Vesencumab Human monoclonal Antineoplastic Neuropilin1 (NRP1)
MNRP1685A antibody IgG1mab Solid malignancies
Phase I 2011 proteinuria
Visilizumab Nuvion Humanized monoclonal Disease modifying CD3
antibody IgG2 Prevent GVHD
Not effective in UC
Vobarilizumab Humanize monoclonal Disease modifying Nothing in PubMed IL6R
scFv inflammatory autoimmune
diseases
Volociximab Chimeric monoclonal Antineoplastic Integrin a5b1
M200 antibody IgG4k Solid tumors
NSCLC phase I/II 2010
Disease modifying phase I
AMD terminated no results
Vopratelimab Humanized monoclonal Antineoplastic Intravenous Inducible T-cell
JTX-2011 antibody IgG1k Solid tumors phase II 2022 costimulator (ICOS)
Vorsetuzumab Humanized monoclonal Antineoplastic Intravenous CD70
mafodotin antibody Phase I 2017
H1F6
SGN-70
Votumumab HumaSPECT Human monoclonal Diagnostic Tumor antigen
Diagnostic antibody Human colon cancer imaging Cytokeratin tumor-
EU 1998 associated antigen
Withdrawn from (CTAA16.88)
market 2003
 Vunakizumab Humanized monoclonal Disease modifying Subcutaneous Interleukin 17 alpha
SHR-1314 antibody IgG1 Psoriasis phase II 2019 Nothing published
Xentuzumab Humanized monoclonal Antineoplastic Intravenous Insulin-like growth factor
BI-836845 antibody Breast, prostate, solid phase I No clinical studies (IGF1, IGF2)
2019 published
XMAB-5574 FDA review Humanized monoclonal Antineoplastic Intravenous CD19
Tafasitamab possible 2019 immunoglobulin fragment Diffuse large B-cell lymphoma
MOR00208 k Fc phase II 2015/18/19/22
phase III 2022
Zalutumumab HuMax-EGFr Human monoclonal Antineoplastic Intravenous EGFR
2F8 Suspended for antibody Squamous cell carcinoma of

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

HUMAX-EGFR commercia- the head and neck phase II
lization 2011
phase III 2016
Zanolimumab HuMax-CD4 Humanized monoclonal Antineoplastic CTCL Intravenous CD4
(trade name) antibody IgG1k Phase II good results
Phase III suspended by
company?
Zenocutuzumab Humanized monoclonal Antineoplastic ERBB3, HER3
antibodyIgG1 bispecific
epidermal growth factor
receptors her2,her3
Ziralimumab Human monoclonal Disease modifying No studies clinical trials or CD147 (basigin)
antibody IgM immunosuppressive PubMed
Zolbetuximab Chimeric monoclonal Antineoplastic gastric cancer Intravenous Claudin protein
IMAB362 antibody IgG1k ADCC phase I, IIb (CLDN18.2)
Claudiximab enhance antibody Phase III 2023
Gastrointestinal
adenocarcinomas and
pancreatic tumor
Zolimomab Orthozyme CD 5 Human monoclonal Disease modifying Not effective in preventing CD5
aritox plus antibody IgG1 GVHD 1994
H65-RTA
ZX-CD5

Auristatins are water-soluble dolastatin analogs of dolastatin 10. Dolastatin 10 belongs to dolastatin family and it can powerfully bind to tubulin, thus inhibiting polymerization mediated
through the binding to the vinca alkaloid-binding domain, and causes cell to accumulate in metaphase arrest.

327
328 Immunologic Concepts in Transfusion Medicine

Ankylosing Spondylitis lipoprotein (LDL) and cholesterol levels by 60% even

Certolizumab pegolis is also approved for use with after statin therapy. Hazard ratios for primary and sec-
ankylosing spondylitis. ondary endpoints were less than one (w0.80e0.85)
with fewer cardiovascular-related death or infarction
Systemic Lupus Erythematosus and stroke.288,289
Belimumab (Benlysta) is a human Mab (IgG1l) that Under future watch is frovocimab (LY3015014) a
binds to B-cell activating factor and acts as a B- humanized Mab (IgG4k) with specificity to PCSK9
lymphocyte stimulator-specific inhibitor. It was that completed phase I and II trials. There was up to
approved by the FDA in 2011 for treatment of adult pa- 50% reduction in LDL cholesterol levels. Phase III
tients with active, autoantibody-positive SLE receiving studies have yet to be performed.290
standard therapy. This medication also decreases An additional antibody is lodelcizumab a human-
episodic frequency of lupus nephritis.281e283 ized Mab (IgG1k); however, no studies were found in
[Link] or in Pubmed searches.
Cardiovascular Disease Bococizumab is a humanized Mab (IgG2k) that was
Despite marked improvement in survival from cardio- in phase III trial, which was discontinued secondary to
vascular disease, this illness remains the number one primary endpoints not being achieved.291
cause of mortality in the US. This process causes injury
to the endothelium of blood vessels of the heart second-
ary to toxins, accumulation of cholesterol, or chronic NEUROLOGIC DISEASES
low-grade inflammation. Treatment has been preven- Besides autoimmune and malignant diseases of the
tive, primarily during actual injury or following injury. neurologic system, there are also diseases of the central
Therapies involve changes in behavior (diet, exercise, nervous system classified as degenerative. Such diseases
and cessation of tobacco use), pharmacologic to control include supranuclear palsy (SNP), Alzheimer’s, and Par-
contributing underlying illness (hypercholesterolemia, kinson’s. Alzheimer’s is likely the most common cause
hypertension, diabetes type I and II), to diminish injury of dementia first described in 1907. This disease may
through thrombolytics, stents, vasodilators, supple- be depicted as presenile or senile dementia and pro-
mental oxygen, or to control sequelae of infarctions gresses at a similar rate no matter age of onset. This dis-
(cardiac dysfunction/failure). Passive antibody thera- ease has a genetic predisposition causing it to occur in
pies are being tried to decrease the effects of some of younger age groups. Histological changes include
the contributing factors of atherosclerotic plaque diffuse plaques (containing amyloid), neurofibrillary
formation. plaques, and neuronal loss especially in the hippocam-
Abciximab (ReoPro) is a chimeric recombinant pus and temporal regions. Medical management may
monoclonal fragment (IgG1 Fab’) with specificity to reverse some of the symptoms but does not prevent dis-
platelet glycoprotein IIb/IIIa receptor (CD41 7E3)/Inter- ease progression. Parkinson’s is a mainly sporadic
grin a-IIb that prevents platelets from binding to fibrin- degenerative disease with a gradual progressive course
ogen. This Mab also prevents coagulation factor XIII mainly affecting motor function more than memory.
from binding to platelets allowing stabilization of clots It was first described in 1817. This is a disease of the
and are more easily lysed. The Fc portion of the antibody substantia nigra characterized by loss of melanin con-
is removed to decrease thrombocytopenias. This anti- taining nerve cells and eosinophilic intracytoplasmic in-
body is used during high-risk coronary intervention to clusions. Aside from emotional support and physical
prevent clot formation and cardiac ischemia.284 therapy, medical therapy is used to decrease tremors
Alirocumab (Praluent) is a human Mab (IgG1) with including anticholinergic drugs for tremors at onset,
specificity to proprotein convertase subtilisin/kexin type beta blockers for intention tremors, and levodopa for
9. This medication is used to control cholesterol levels postural imbalance and akinesia. Deep brain stimula-
in patients at high risk for cardiovascular events and tion is also used to treat symptoms later on as disease
in patients with familial hypercholesterolemia who progresses. SNP starts in the same age range as Parkin-
are not controlled by other agents.285e287 son’s (middle to later in life) that was first described
Evolocumab (Repatha) is a human Mab (IgG2l) in 1963 with disturbances in gait and balance secondary
FDA approved for the treatment of hypercholesterole- to rigidity of trunk muscles. Loss of neurons and gliosis
mia in patients with familial hypercholesterolemia or is seen in the midbrain. Medical treatment is relatively
history of cardiovascular disease. This Mab has speci- unsuccessful. Multiple sclerosis is a demyelinating dis-
ficity to PCSK9. This medication reduced low-density ease most often seen in young adults. The clinical
 CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies 329

manifestations are diverse and the progression can be Alzheimer's Disease

chronic, acute, or remitting and relapsing. Medications Aducanumab is a human Mab IgG1 with specificity to
and therapeutic plasma exchange have been used to b-amyloid (N-terminus 3e6) soluble oligomers and
treat this debilitating disease with limited efficacy. Clin- insoluble fibers. Phase III clinical trials are ongoing
ical trials are ongoing looking at Mab therapies for treat- since 2015.
ment of these four neurologic degenerative diseases. BAN-2401 is a humanized Mab IgG1 with specificity
to b-amyloid fibrillary and soluble b amyloid and is in
Multiple Sclerosis phase IIb clinical studies since 2013.
Alemtuzumab (Lemtrada) is a humanized Mab Gosuranemab (BIIB092, IPN-007) is a humanized
(IgG1k) targeting CD52 that depletes lymphocytes (B Mab IgG4k with specificity to the tau protein and is in
and T cell) as reported earlier and is FDA approved clinical trials to treat Alzheimer’s disease scheduled to
for treatment of acute relapsing and remitting multiple be completed in 2021. Gosuranemab is also in phase
sclerosis.292 I studies to treat progressive suranuclear palsy and will
Ocrelizumab (Ocrevus) is a humanized Mab be completed in 2020.
(IgG1k) with specificity to CD20 (a B-cell membrane Crenezumab (RG7412, MABT5102A) is a human-
protein). In phase II trials, there were decreases in ized Mab IgG4 with specificity to 1e40 b-amyloid
brain lesions on imaging, and decrease rate of and is on phase III studies scheduled to be completed
disability decline in primary progressive multiple in 2021 and 2022.
sclerosis.293 Gantenerumab (R04909832, R1450) is a human
Natalizumab (Tysabri) is a monoclonal IgG4k hu- Mab IgG1k with targets b-amyloid. This Mab on initial
manized antibody with specificity to cell adhesion phase III studies was found to be ineffective. Ongoing
molecule (CD62L) that is FDA approved for relapsing phase II/III trials are currently in place at higher dosing
multiple sclerosis.294,295 in a clinical population of people with autosomal
The mabs to watch out for in the future and are in dominant form of Alzheimer’s disease.
clinical trials include anifrolumab a human mono- Solanezumab (LY2062430) is a humanized Mab
clonal antibody in phase I trials; elezanumab is a hu- IgG1 with specificity to beta amyloid. Initial phase III
man Mab (IgG1l) with specificity to repulsive trials discontinued for lack of efficacy in preventing Alz-
guidance molecule family member-A that is in phase heimer’s disease. Ongoing phase III trials are now in
II trials to be completed 2021; and finally inebilizu- place for secondary prevention of this disease and will
mab (MEDI-551) is a humanized monoclonal anti- be completed in 2021 and 2022.
body (IgG2k) with specificity to CD19 (a B-cell Mab antibodies studied and were ineffective include
lymphocyte protein). This Mab mechanism of action bapineuzumab, gantenerumab (R04909832, R1450),
is via ADCC and has completed phase I trials with and ponezumab (RN1219, PF-04,360,365).
good safety profile and response in decreasing lesions
seen on contrast enhanced magnetic resonance imag- Parkinson's Disease
ing. Otilimabis (MOR103) is a human Mab (IgG1l) Prasinezumab (PRX002, RG7935, RO7046015) is a hu-
completing phase I studies with good safety profile manized Mab IgG1k with specificity to a-synuclein.
that targets granulocyte-macrophage colony- This Mab is in phase II clinical trials to treat Parkinson’s
stimulating factor. Ublituximab is in phase II clinical and will be completed in 2021.
studies to be completed in 2019, and phase III studies
are scheduled to be completed in 2021. This Mab is a
chimeric Mab (IgG1k) with specificity to CD20 ALLERGIC DISEASES
MS2A1.296e300 Allergic reactions develop because of immunologic stim-
Additional Mab have serious adverse effects such as ulation of IgE antibodies followed by their interaction
daclizumab a humanized monoclonal (IgG1k) with with allergens and mast cells. Effects can be local (derma-
specificity to (CD25 {IL-2Ra}); or are ineffective as is titis) or systemic (respiratory, cardiovascular, and gastro-
opicinumab a human Mab IgG1 with specificity to intestinal). Treatment is either avoidance of the allergens
Leucine-rich repeat and immunoglobulin domain con- or supportive therapy in acute allergic reactions
taining neurite outgrowth inhibitor receptor interacting including pharmacologic treatment with type 1 and 2
protein-1 which in a phase II trial was no more benefi- histamine blockers, glucocorticosteroids, and if life-
cial than placebo in treating optic neuritis in multiple threatening epinephrine. Passive antibody therapies are
sclerosis patients.301,302 being studied and approved to curtail severe reactions.
330 Immunologic Concepts in Transfusion Medicine

Asthma an inherited deficiency of ADAMTS-13. This patient

Asthma affects 24 million individuals in the US, and up population with congenital deficiency is managed
to 10% of asthma patients have severe disease that may with transfusion of FFP to replace the deficient enzyme.
be uncontrolled despite high doses of standard-of-care Acquired TTP is typically treated with therapeutic
asthma medications requiring additional use of chronic plasma exchange (TPE). This treatment modality
oral corticosteroids. Benralizumab (Fensenra) is a hu- removes the inhibitory antibody and ultralarge vWF
manized Mab (IgG1k) with specificity to CD125 (IL- multimers. Similarly, TPE will replete the missing
5Ra). This Mab is approved to treat severe asthma of enzyme. Immunosuppressive agents may be added if
the eosinophilic subtype in ages 12 and older. Its mech- only TPE is not effective. A Mab preventing interaction
anism of action is to decrease the number of eosino- of vWF and platelets was recently approved for use in
phils via ADCC. Basophils are also depleted.303 treating this disorder.305,306 Caplacizumab-yhdp
(Cablivi) is a humanized single-variable-domain
Atopic Dermatitis immunoglobulin (Nanobody) that inhibits the interac-
Dupilumab (Dupixent) is a human monoclonal gG4 tion between ultralarge vWF multimers and platelets
antibody with specificity to interleukin-4 receptor and is directed against vWF. It induces a faster response
subunit-alpha (IL-4Ra) that is approved to treat severe to therapy with TPE and decreases relapse with
atopic dermatitis in adults.304 continued use during TPE. This medication is then
used post-TPE treatment until immunological evidence
of disease is controlled to prevent relapse.305,307,308 This
COAGULOPATHY AND OTHER BENIGN medication was FDA approved for use in TTP in 2019.
HEMATOLOGIC DISEASES Atypical hemolytic uremic syndrome (aHUS) is a
Coagulopathies are usually either autoimmune or ge- disorder of the complement system due to uncontrolled
netic. In factor VIII deficiency, recombinant factor VIII activation. This disorder presents with thrombocyto-
is used to replace lack of this protein. However, patients penia, thrombi, and renal dysfunction. Historically,
may develop antibodies to factor VIII leading to high ti- this illness was treated with TPE; however, end-stage
ters of inhibitors. Furthermore, patients without defi- renal failure occurred in 30% of patients and about
ciency may also develop autoantibodies to factor VIII 65% mortality in subsequent relapses with increasing
de novo leading to coagulopathies. Other factor combi- incidence of renal failure. There are now two mono-
nations as well as recombinant active factors have been clonal antibodies approved for the treatment of
created to overcome these inhibitory antibodies. Mabs aHUS. Refer to Table 16.1.
with bispecific binding are also being researched as
another avenue for treatment. Sickle Pain Crisis
ITP can lead to critical low platelet levels increasing In sickle cell disease, one of the frequent complications
risk for severe bleeding. ITP can occur in both adult is pain crises. This is usually treated with analgesics, ox-
and pediatric settings as it is considered an autoimmune ygen, hydration, and transfusions (simple or exchange).
disease. Typically, this is treated with steroids and IVIG. Monoclonal antibodies are being developed to treat
In addition, as mentioned earlier, RhDþ patients have pain crises in sickle cell patients in both adult and pedi-
benefitted from polyclonal medications directed against atric populations. Crizanlizumab is a humanized Mab
the D antigen. Recently, Mab to treat this disease have (IgG2k) with specificity to selectin P. One phase II trial
been developed and will be discussed next. was completed in 2016 and three additional phase II
Thrombotic thrombocytopenic purpura (TTP) is a studies will be completed between 2021 and 27 to treat
blood disorder that does not lead to bleeding but to vasoocclusive pain crisis. This medication may be under
development of diffuse thrombi in small blood vessels. FDA review as early as 2019.309,310
More often, this disorder is secondary to an autoim-
mune inhibitory antibody to the disintegrin and metal-
loproteinase with thrombospondin type 1 motif INFECTIONS
member-13 (ADAMTS-13), known as acquired TTP. Antimicrobials have historically been developed against
Inhibiting this zinc containing metalloprotease leads a variety of viral, bacterial, fungal, and parasitic infec-
to lack of cleavage of large multimers of von Willebrand tions. These pharmaceuticals target differences from hu-
Factor (vWF). The large vWF multimers then more man cells of these particular organisms such as cell wall
easily bind to platelets resulting in platelet clots in small or membrane structure, genetic make-up, transcription/
blood vessels. More rarely, this disorder is secondary to translation of genetic material, or metabolic pathways.
 CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies 331

Often organisms develop resistance to entire categories previously studied but usually the virus mutates quickly
of these medications. Earlier in the chapter, passive and the infection is not controlled. More recently, in
polyclonal antibodies were discussed in the treatment clinical trials, cocktails of Mabs are being tried to
of some of these infectious agents and we will now more closely mimic the benefits of polyclonal therapies.
discuss research in monoclonal therapies to pathogenic These Mabs include foravirumab, rafivirumab (CR57),
microorganisms. and Rmab.

Clostridium difficile Hepatitis B virus

Enterocolitis from Clostridium difficile is a community or HBV is one of if not the most common infections in the
hospital acquired infection increasing morbidity and world. Even though antivirals are available and effec-
mortality in those that acquire it. Treatment is support- tive, only recently they have they been widely used in
ive or with fecal transplants or antibiotics. Bezlotoxu- the infant population and not just “high”-risk individ-
mab (Zinplava) is a human Mab (IgG1) with uals. Mabs to treat this infection that are being investi-
specificity to Clostridium difficile’s B toxin. It is used to gated include libivirumab. Mab that is not found to
treat pseudomembranous colitis and prevent be effective is tuvirumab.
C. difficile reinfection.311,312
Actoxumab, a monoclonal antibody against Ebola
C. difficile toxin A, has shown not to be clinically Ebola is a relatively rare but devastating hemorrhagic
significant. infection. Most care is supportive with various studies
being performed to prevent/mitigate this disease. Vac-
Respiratory Syncytial Virus cines are under development as well as passive poly-
Respiratory syncytial virus (RSV) infects almost all chil- clonal therapies. Mab therapies being developed or
dren by 2 years old and poses extra risk in preterm in- studied include porgaviximab (C2G4), cosfroviximab,
fants. Supportive therapy, RSV-IG or IVIG, and and larcaviximab.
antiviral therapy have been used to mitigate the sequela For these and other bacterial, fungal, and viral anti-
of this infection with optimal response yet to be seen. infectious agents, information may be found in
No vaccines have yet to be developed for this infection. Table 16.1.
Recently, monoclonal antibodies have been FDA
approved or are undergoing pre/clinical trials to treat
this infectious process and include palivizumab, Nirse- IMMUNOMODULATION
vimab (MEDI8897), TRL3d3 (3D3), and ALX- In solid organ transplants, cellular or humoral immu-
0171.313,314 nity can develop against the transplant leading to acute
Not beneficial or safe in use for RSV: motavizumab, or chronic rejection. An additional complication with
Suptavumab (REGN2222, SAR438584). these and stem cell transplants is severe GVHD. In the
past, these transplant complications were treated with
Influenza virus high-dose glucocorticosteroids, immunosuppressive
Influenza is a worldwide respiratory infectious problem medication, chemotherapeutic agents, IVIG, or T-cell
with cyclic epidemics yearly. Supportive therapy, yearly lymphocytic specific immunoglobulins. Recently,
vaccinations, and antivirals are used to decrease the Mabs have been added to this armamentarium to better
morbidity and mortality caused by this sometimes viru- control these adverse reactions to transplantations.
lent pathogen. Both polyclonal and monoclonal thera- Basiliximab (Simulect) is a chimeric Mab (IgG1k)
pies are being evaluated to better treat these infections. with specificity to CD25 IL-2a. The only FDA-
Mabs in pre/clinical trials include diridavumab approved indication for this medication is prophylaxis
(CR6262), firivumab, gedivumab (RG7745, of acute rejection in renal transplant patients. There
RO6876802), lesofavumab (RG70026), and Navivu- are multiple ongoing studies of this biological for other
mab (CT-P27). organ transplants including liver, lung, and heart as well
as for inflammatory/immunologic diseases such as
Rabies GVHD following stem cell transplantation, ulcerative
Rabies is a devastating viral infection with swift mortal- colitis, and uveitis.315e319
ity if not treated quickly after initial exposure. Vaccines Belatacept (Nulojix) is a soluble fusion protein con-
usually react too slowly and have to be combined with sisting of the modified extracellular domain of CTLA-4
polyclonal IVIG infusions. Monoclonal therapy was fused to the Fc domain of a recombinant human Mab
332 Immunologic Concepts in Transfusion Medicine

IgG1. This Mab selectively inhibits T-cell activation stimulate islet cells to produce more insulin. Mabs are
through costimulation blockade binding to both being developed to potentially mitigate the autoim-
CD80 and CD86 while blocking CD28 via tighter bind- mune process leading to Type I diabetes mellitus or
ing than its parent antibody abatacept. Refer to the sequela of renal failure often seen with this disease.
Table 16.1. For type II, Mabs are being investigated to potentially
decrease body mass index and thus decrease disease
severity. Refer to Table 16.1.
METABOLIC SYNDROMES
Hypercholesterolemia is associated with increased risk
for cardiovascular disease/atherosclerosis secondary to OTHER CLINICAL DISORDERS
inherited or dietary etiologies. Diet and exercise are Age-related macular degeneration (AMD) is the leading
used to treat mild forms of these disorders. Medications irreversible cause of visual loss affecting the elderly. Two
such as nicotinic acid, fibrates, bile acid binding resins, forms include a dry form with deposits in the macula or
and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase a wet form involving abnormal growth of blood vessels.
inhibitors are used for more severe forms of these disor- The wet form, even though less frequent, is associated
ders. Phase III studies have been completed with mono- with more severe visual acuity loss. Antiangiogenesic
clonal antibodies for patients’ refractory to the drugs or laser treatments are used to slow the progres-
previously mentioned forms of therapy. sion or even partially reverse visual loss. Some trials
have been completed while others are ongoing using
Hypophosphatemia Mab to treat the wet form of AMD. Brolucizumab was
Burosumab (KRN23, Crysvita) is a human Mab IgG1k found as good as if not better than aflibercept in a phase
with specificity to phosphaturic hormone fibroblast III clinical trial.327
growth factor 23 (FGF 23). This hormone is a regulator Cryopyrin-associated periodic syndromes (including
of phosphate and vitamin D homeostasis. FGF23 in- familial cold auto-inflammatory syndrome and
hibits the enzyme CYP27B1 and stimulates CYP24A1, Muckle-Wells syndrome); tumor necrosis factor
thereby reducing circulating levels of 1,25- receptor-associated periodic syndrome (TRAPS); hyper-
dihydroxyvitamin D (1,25(OH)2D), the active metabo- immunoglobulin D Syndrome (HIDS)/mevalonate ki-
lite of vitamin D. This medication is FDA approved for nase deficiency and familial Mediterranean fever
the treatment of X-linked hypophosphatemic (FMF) may also respond to canakinumab.328
rickets.320,321

Osteoporosis POTENTIAL FUTURE USES OF

Denosumab (Prolia) is an FDA-approved human Mab MONOCLONAL ANTIBODIES AND THEIR
(IgG2) that is a receptor activator of nuclear factor kB TARGETS
ligand that inhibits development and activity of osteo- Passive antibody therapy continues to be useful clini-
clasts. As Prolia, this medication is used to prevent or cally whether polyclonal or monoclonal therapy is
treat osteoporosis in women.322e324 This medication implemented. Increased utilization of the classic poly-
under the trade name Xgeva is also used to prevent clonal antibody preparations continue especially in
skeletal-related events in adults with bone metastasis the realm of infections. In the past 3 years, monoclonal
from breast, prostate cancers, and multiple therapy has evolved and revolutionized treatment in
myeloma.325,326 many areas. As targets are identified to modify disease
pathology no matter its genre we continue to get a better
handle on morbidity and mortality. We are learning
ENDOCRINE DISORDERS that not only is the target important put the portion
Diabetes may be classified as primary or secondary. In of the target mediating the effect we intend to modify
this chapter, we will be mainly interested in both is also important. Importantly, modification of anti-
insulin-dependent (Type I) and insulin-independent bodies to be more compatible with the immune system
types (Type II). Type I diabetes mellitus is generally sec- while decreasing rapidity of clearance also allows for
ondary to loss of b cells in the islets of Langerhans and more consistent therapy. There are also many targets
subsequent loss of insulin production. Type II typically yet to be discovered or only now being developed as
is secondary to decreased sensitivity to the effects of in- in the canonical wingless/integrated (WNT) signaling.
sulin. In type I, insulin is replaced exogenously depend- This receptor family is important in a multitude of dis-
ing on glucose levels. In type II, medications are given to eases not limited to: hereditary colorectal cancer,
TABLE 16.2
Summary of Polyclonal Antibody Therapies.
AHFS
Generic Drug Name Brand Name Additional Brand Names Classification Dosage Form(s) Restricted Medication
Antithymocyte globulin Atgam Immunosuppressive Intravenous solution

CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies

(equine) agent
Antithymocyte globulin Thymoglobulin Immunosuppressive Intravenous solution
(rabbit) agent
Antivenin Latrodectus Black widow Serums Intravenous solution
mactans Antivenin
Antivenin micrurus Eastern and Serums Intravenous solution
Texas coral
Snake
Antivenin
Botulism immune globulin BabyBIG
Crotalidae polyvalent Crofab Serums Intravenous solution
immune Fab
Cytomegalovirus immune Cytogam Serums Intravenous solution Yes
globulin
Digoxin immune Fab Digibind Serums Intravenous solution
Hepatitis B immune globulin Hepagam-B Serums Intramuscular solution,
Intravenous solution
Hepatitis B immune globulin BayHepB HepaGam B, Hyper Hep B,
Nabi-HB
High antibody titer Ebola FFP
High antibody titer influenza
FFP
Continued

333
 334
TABLE 16.2
Summary of Polyclonal Antibody [Link]'d
AHFS

Immunologic Concepts in Transfusion Medicine

Generic Drug Name Brand Name Additional Brand Names Classification Dosage Form(s) Restricted Medication
Immunoglobulin (generic) Gamunex Vivaglobin, Cuvitru, Intravenous, Treat XLA, CVID, Hyper
Privigen, gammagard, Subcutaneous IgM syndromes, Wiskott
octagam, gamunex, Aldrich syndrome
hizentra, Bivigam,
Carimune, Flebogamma,
Gamastan, Gamimune,
Gammaplex, gammar,
Panglobulin, Panzyga,
Sandoglobulin
Rabies immune globulin Bayrab HyperRAB, Imogam
rabies, KedRAB
Respiratory syncytial virus RespiGam
immune globulin
Rho (D) immune globulin WhinRho Rhophylac, MicRhoGAM, Serums Intravenous,
RhoGam BatRhoD, HyperRho intramuscular solutions
Rimabotulinumtoxin B Myobloc Other Miscellaneous Injection solution Yes
Therapeutic agents
Rozrolimupab Anti-RhD
Prevent
isoimmunization
ITP
Tetanus immune globulin Baytet Hypertet
Varicella zoster immune VariZIG
globulin

Searched sites for table information. Monoclonal. [Link] [Link] [Link]

gov/ct2/. [Link] [Link] [Link] [Link]
 CHAPTER 16 Passive Monoclonal and Polyclonal Antibody Therapies 335

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17. Wohlman MH, Toledo-Pereyra LH, Zeichner WD. The
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