Monoclonal antibody therapy

Source: Wikipedia, the free encyclopedia.
Each antibody binds only one specific antigen.

cytotoxic
radiation).

Major applications include

blood clot
prevention, and certain infections.

Antibody structure and function

Further information:
Monoclonal antibodies

Fc (fragment crystallizable region) part of the molecule. The Fab fragments contain the variable domains, which consist of three antibody hypervariable amino acid domains responsible for the antibody specificity embedded into constant regions. The four known IgG subclasses are involved in antibody-dependent cellular cytotoxicity.[2]
active immunity. The advantage of active monoclonal antibody therapy is the fact that the immune system will produce antibodies long-term, with only a short-term drug administration to induce this response. However, the immune response to certain antigens may be inadequate, especially in the elderly. Additionally, adverse reactions from these antibodies may occur because of long-lasting response to antigens.[4] Passive monoclonal antibody therapy can ensure consistent antibody concentration, and can control for adverse reactions by stopping administration. However, the repeated administration and consequent higher cost for this therapy are major disadvantages.[4]

Monoclonal antibody therapy may prove to be beneficial for

autoimmune diseases, and neurological disorders that result in the degeneration of body cells, such as Alzheimer's disease. Monoclonal antibody therapy can aid the immune system because the innate immune system responds to the environmental factors it encounters by discriminating against foreign cells from cells of the body. Therefore, tumor cells that are proliferating at high rates, or body cells that are dying which subsequently cause physiological problems are generally not specifically targeted by the immune system, since tumor cells are the patient's own cells. Tumor cells, however are highly abnormal, and many display unusual antigens. Some such tumor antigens are inappropriate for the cell type or its environment. Monoclonal antibodies can target tumor cells or abnormal cells in the body that are recognized as body cells, but are debilitating to one's health.[citation needed
]

History

scFv, single-chain Fv fragment.[5]

malignant neoplasms found mAb therapy of limited and generally short-lived success with blood malignancies.[8][9] Treatment also had to be tailored to each individual patient, which was impracticable in routine clinical settings.[citation needed
]

Four major antibody types that have been developed are

murine, chimeric, humanised and human. Antibodies of each type are distinguished by suffixes on their name.[citation needed
]

Murine

Initial therapeutic antibodies were murine

analogues (suffix -omab). These antibodies have: a short half-life in vivo (due to immune complex formation), limited penetration into tumour sites and inadequately recruit host effector functions.[10] Chimeric and humanized antibodies have generally replaced them in therapeutic antibody applications.[11] Understanding of proteomics has proven essential in identifying novel tumour targets.[citation needed
]

Initially, murine antibodies were obtained by hybridoma technology, for which Jerne, Köhler and Milstein received a Nobel prize. However the dissimilarity between murine and human immune systems led to the clinical failure of these antibodies, except in some specific circumstances. Major problems associated with murine antibodies included reduced stimulation of

transgenic mice and phage display.[11]

Chimeric and humanized

To reduce murine antibody

serum half-life.[citation needed
]

Humanised antibodies are produced by grafting murine hypervariable regions on amino acid domains into human antibodies. This results in a molecule of approximately 95% human origin. Humanised antibodies bind antigen much more weakly than the parent murine monoclonal antibody, with reported decreases in affinity of up to several hundredfold.

site-specific mutagenesis.[15]

Human monoclonal antibodies

Human monoclonal antibodies (suffix -umab) are produced using

immunoglobulin genes into the murine genome and vaccinating the transgenic mouse against the desired antigen, leading to the production of appropriate monoclonal antibodies.[11] Murine antibodies in vitro are thereby transformed into fully human antibodies.[3]

The heavy and light chains of human IgG proteins are expressed in structural polymorphic (allotypic) forms. Human IgG allotype is one of the many factors that can contribute to immunogenicity.[16][17]

Targeted conditions

Cancer

Anti-cancer monoclonal antibodies can be targeted against malignant cells by several mechanisms. Ramucirumab is a recombinant human monoclonal antibody and is used in the treatment of advanced malignancies.[18] In childhood lymphoma, phase I and II studies have found a positive effect of using antibody therapy.[19]

Monoclonal antibodies used to boost an anticancer immune response is another strategy to fight cancer where cancer cells are not targeted directly. Strategies include antibodies engineered to block mechanisms which downregulate anticancer immune responses, checkpoints such as PD-1 and CTLA-4 (checkpoint therapy),[20] and antibodies modified to stimulate activation of immune cells.[21]

Autoimmune diseases

Monoclonal antibodies used for

rejection of kidney transplants.[22] Omalizumab inhibits human immunoglobulin E (IgE) and is useful in moderate-to-severe allergic asthma.[citation needed
]

Alzheimer's disease

Alzheimer's disease (AD) is a multi-faceted, age-dependent, progressive neurodegenerative disorder, and is a major cause of dementia.

Amyloid hypothesis, the accumulation of extracellular amyloid beta peptides (Aβ) into plaques via oligomerization leads to hallmark symptomatic conditions of AD through synaptic dysfunction and neurodegeneration.[24] Immunotherapy via exogenous monoclonal antibody (mAb) administration has been known to treat various central nervous disorders. In the case of AD, immunotherapy is believed to inhibit Aβ-oligomerization or clearing of Aβ from the brain and thereby prevent neurotoxicity.[25]

However, mAbs are large molecules and due to the blood–brain barrier, uptake of mAb into the brain is extremely limited, only approximately 1 of 1000 mAb molecules is estimated to pass.[25] However, the Peripheral Sink hypothesis proposes a mechanism where mAbs may not need to cross the blood–brain barrier.[26] Therefore, many research studies are being conducted from failed attempts to treat AD in the past.[24]

However, anti-Aβ vaccines can promote antibody-mediated clearance of Aβ plaques in transgenic mice models with amyloid precursor proteins (APP), and can reduce cognitive impairments.

passive immunotherapy. In this case the antibodies is produced externally in cultured cells and are delivered to the patient in the form of a drug. In mice expressing APP, both active and passive immunization of anti-Aβ antibodies has been shown to be effective in clearing plaques, and can improve cognitive function.[24]

Currently, there are two FDA approved antibody therapies for Alzheimer's disease, Aducanemab and Lecanemab. Aducanemab has received accelerated approval while Lecanemab has received full approval.[25] Several clinical trials using passive and active immunization have been performed and some are on the way with expected results in a couple of years.[24][25] The implementation of these drugs is often during the early onset of AD. Other research and drug development for early intervention and AD prevention is ongoing. Examples of important mAb drugs that have been or are under evaluation for treatment of AD include Bapineuzumab, Solanezumab, Gautenerumab, Crenezumab, Aducanemab, Lecanemab and Donanemab.[25]

Bapineuzumab

vasogenic edema,[28] a cytotoxic condition where the blood brain barrier has been disrupted thereby affecting white matter from excess accumulation of fluid from capillaries in intracellular and extracellular spaces of the brain.[29]

In Phase III clinical trials, Bapineuzumab showed promising positive effect on biomarkers of AD but failed to show effect on cognitive decline. Therefore, Bapineuzumab was discontinued after failing in the Phase III clinical trial.[29]

Solanezumab

Solanezumab, an anti-Aβ mAb, targets the N-terminus of Aβ. In Phase I and Phase II of clinical trials, Solanezumab treatment resulted in cerebrospinal fluid elevation of Aβ, thereby showing a reduced concentration of Aβ plaques. Additionally, there are no associated adverse side effects. Phase III clinical trials of Solanezumab brought about significant reduction in cognitive impairment in patients with mild AD, but not in patients with severe AD. However, Aβ concentration did not significantly change, along with other AD biomarkers, including phospho-tau expression, and hippocampal volume. Phase III clinical trials of Solanezumab failed as it did not show effect on cognitive decline in comparison to placebo. [30]

Lecanemab

Lecanemab (BAN2401), is a humanized mAb that selectively targets toxic soluble Aβ protofibrils,[31] In phase 3 clinical trials,[32] Lecanemab showed a 27% slower cognitive decline after 18 months of treatment in comparison to placebo.[33][34] The phase 3 clinical trials also reported infusion related reactions, amyloid-related imaging abnormalities and headaches as the most common side effects of Lecanemab. In July 2023 the FDA gave Lecanemab full approval for the treatment of Alzheimer's Disease [35] and it was given the commercial name Leqembi.

Preventive trials

Failure of several drugs in Phase III clinical trials has led to AD prevention and early intervention for onset AD treatment endeavours. Passive anti-Aβ mAb treatment can be used for preventive attempts to modify AD progression before it causes extensive brain damage and symptoms. Trials using mAb treatment for patients positive for genetic risk factors, and elderly patients positive for indicators of AD are underway. This includes anti-AB treatment in Asymptomatic Alzheimer's Disease (A4), the Alzheimer's Prevention Initiative (API), and DIAN-TU.[26] The A4 study on older individuals who are positive for indicators of AD but are negative for genetic risk factors will test Solanezumab in Phase III Clinical Trials, as a follow-up of previous Solanezumab studies.[26] DIAN-TU, launched in December 2012, focuses on young patients positive for genetic mutations that are risks for AD. This study uses Solanezumab and Gautenerumab. Gautenerumab, the first fully human MAB that preferentially interacts with oligomerized Aβ plaques in the brain, caused significant reduction in Aβ concentration in Phase I clinical trials, preventing plaque formation and concentration without altering plasma concentration of the brain. Phase II and III clinical trials are currently being conducted.[26]

Therapy types

Radioimmunotherapy

lymphomas, as these are highly radio-sensitive malignancies. To limit radiation exposure, murine antibodies were chosen, as their high immunogenicity promotes rapid tumor clearance. Tositumomab is an example used for non-Hodgkin's lymphoma.[citation needed
]

Antibody-directed enzyme prodrug therapy

Antibody-directed enzyme prodrug therapy (ADEPT) involves the application of cancer-associated monoclonal antibodies that are linked to a drug-activating enzyme. Systemic administration of a non-toxic agent results in the antibody's conversion to a toxic drug, resulting in a cytotoxic effect that can be targeted at malignant cells. The clinical success of ADEPT treatments is limited.[36]

Antibody-drug conjugates

Antibody-drug conjugates (ADCs) are antibodies linked to one or more drug molecules. Typically when the ADC meets the target cell (e.g. a cancerous cell) the drug is released to kill it. Many ADCs are in clinical development. As of 2016 a few have been approved.[citation needed
]

Immunoliposome therapy

Immunoliposomes are antibody-conjugated

liposomes. Liposomes can carry drugs or therapeutic nucleotides and when conjugated with monoclonal antibodies, may be directed against malignant cells. Immunoliposomes have been successfully used in vivo to convey tumour-suppressing genes into tumours, using an antibody fragment against the human transferrin receptor. Tissue-specific gene delivery using immunoliposomes has been achieved in brain and breast cancer tissue.[37]

Checkpoint therapy

Checkpoint therapy uses antibodies and other techniques to circumvent the defenses that tumors use to suppress the immune system. Each defense is known as a checkpoint. Compound therapies combine antibodies to suppress multiple defensive layers. Known checkpoints include

PD-1 targeted by nivolumab and pembrolizumab and the tumor microenvironment.[20]

The

CXCL12-regulated T cell exclusion.[38]

FDA-approved therapeutic antibodies

For a more comprehensive list, see List of therapeutic monoclonal antibodies.
See also: Monoclonal antibody § Therapeutic uses

The first FDA-approved therapeutic monoclonal antibody was a murine IgG2a CD3 specific

clinical trials
. Most are concerned with immunological and oncological targets.

FDA approved therapeutic monoclonal antibodies
Antibody Brand name Company Approval date Route Type Target Indication
(Targeted disease)		 BLA STN Drug Label
abciximab ReoPro
Centocor
 12/22/1994 intravenous chimeric Fab
GPIIb/IIIa
 Percutaneous coronary intervention 103575 Link
adalimumab Humira
Abbvie
 12/31/2002 subcutaneous fully human
TNF
 Rheumatoid arthritis 125057 Link
adalimumab-atto
 Amjevita Amgen 9/23/2016 subcutaneous fully human, biosimilar
TNF
Plaque psoriasis
 761024 Link
ado-trastuzumab emtansine
 Kadcyla Genentech 2/22/2013 intravenous humanized,
antibody-drug conjugate
 HER2 Metastatic breast cancer 125427 Link
alemtuzumab Campath, Lemtrada Genzyme 5/7/2001 intravenous humanized CD52
B-cell chronic lymphocytic leukemia
 103948 Link
alirocumab Praluent
Sanofi Aventis
 7/24/2015 subcutaneous fully human PCSK9 Heterozygous familial hypercholesterolemia
Refractory hypercholesterolemia		 125559 Link
atezolizumab Tecentriq Genentech 5/18/2016 intravenous humanized PD-L1
Urothelial carcinoma
 761034 Link
atezolizumab Tecentriq Genentech 10/18/2016 intravenous humanized PD-L1
non-small cell lung cancer
 761041 Link
avelumab Bavencio
EMD Serono
 3/23/2017 intravenous fully human PD-L1 Metastatic
Merkel cell carcinoma
 761049 Link
basiliximab Simulect Novartis 5/12/1998 intravenous chimeric IL2RA Prophylaxis of
renal transplant
 103764 Link
belimumab Benlysta Human Genome Sciences 3/9/2011 intravenous fully human
BLyS
Systemic lupus erythematosus
 125370 Link
bevacizumab Avastin Genentech 2/26/2004 intravenous humanized
VEGF
 Metastatic colorectal cancer 125085 Link
bezlotoxumab Zinplava Merck 10/21/2016 intravenous fully human
Clostridium difficile toxin B
 Prevent recurrence of
Clostridium difficile infection
 761046 Link
blinatumomab Blincyto Amgen 12/3/2014 intravenous mouse, bispecific CD19
Precursor B-cell acute lymphoblastic leukemia
 125557 Link
brentuximab vedotin Adcetris
Seattle Genetics
 9/19/2011 intravenous chimeric,
antibody-drug conjugate
 CD30 Hodgkin lymphoma
Anaplastic large-cell lymphoma		 125388 Link
brodalumab Siliq
Valeant
 2/15/2017 subcutaneous chimeric IL17RA
Plaque psoriasis
 761032 Link
canakinumab Ilaris Novartis 6/17/2009 subcutaneous fully human
IL1B
 Cryopyrin-associated periodic syndrome 125319 Link
capromab pendetide
 ProstaScint Cytogen 10/28/1996 intravenous murine, radiolabeled PSMA Diagnostic imaging agent in newly diagnosed prostate cancer or post-prostatectomy 103608 Link
certolizumab pegol Cimzia UCB (company) 4/22/2008 subcutaneous humanized
TNF
 Crohn's disease 125160 Link
cetuximab Erbitux ImClone Systems 2/12/2004 intravenous chimeric EGFR Metastatic
colorectal carcinoma
 125084 Link
daclizumab Zenapax
Roche
 12/10/1997 intravenous humanized IL2RA Prophylaxis of
renal transplant
 103749 Link
daclizumab Zinbryta Biogen 5/27/2016 subcutaneous humanized
IL2R
 Multiple sclerosis 761029 Link
daratumumab Darzalex
Janssen Biotech
 11/16/2015 intravenous fully human CD38 Multiple myeloma 761036 Link
denosumab Prolia, Xgeva Amgen 6/1/2010 subcutaneous fully human RANKL
Postmenopausal women with osteoporosis
 125320 Link
dinutuximab Unituxin United Therapeutics 3/10/2015 intravenous chimeric GD2 Pediatric high-risk neuroblastoma 125516 Link
dupilumab Dupixent Regeneron Pharmaceuticals 3/28/2017 subcutaneous fully human
IL4RA
 Atopic dermatitis, asthma 761055 Link
durvalumab Imfinzi AstraZeneca 5/1/2017 intravenous fully human PD-L1
Urothelial carcinoma
 761069 Link
eculizumab Soliris Alexion 3/16/2007 intravenous humanized Complement component 5 Paroxysmal nocturnal hemoglobinuria 125166 Link
elotuzumab Empliciti
Bristol-Myers Squibb
 11/30/2015 intravenous humanized SLAMF7 Multiple myeloma 761035 Link
evolocumab Repatha Amgen 8/27/2015 subcutaneous fully human PCSK9 Heterozygous familial hypercholesterolemia
Refractory hypercholesterolemia		 125522 Link
golimumab Simponi
Centocor
 4/24/2009 subcutaneous fully human
TNF
 Rheumatoid arthritis
Psoriatic arthritis
Ankylosing spondylitis		 125289 Link
golimumab Simponi Aria
Janssen Biotech
 7/18/2013 intravenous fully human
TNF
 Rheumatoid arthritis 125433 Link
ibritumomab tiuxetan Zevalin Spectrum Pharmaceuticals 2/19/2002 intravenous murine, radioimmunotherapy CD20 Relapsed or refractory low-grade, follicular, or transformed B-cell
non-Hodgkin's lymphoma
 125019 Link
idarucizumab Praxbind Boehringer Ingelheim 10/16/2015 intravenous humanized Fab dabigatran Emergency reversal of anticoagulant dabigatran 761025 Link
infliximab Remicade
Centocor
 8/24/1998 intravenous chimeric
TNF alpha
 Crohn's disease 103772 Link
infliximab-abda
 Renflexis
Samsung Bioepis
 4/21/2017 intravenous chimeric, biosimilar
TNF
Plaque psoriasis
 761054 Link
infliximab-dyyb
 Inflectra
Celltrion Healthcare
 4/5/2016 intravenous chimeric, biosimilar
TNF
Plaque psoriasis
 125544 Link
ipilimumab Yervoy
Bristol-Myers Squibb
 3/25/2011 intravenous fully human
CTLA-4
Metastatic melanoma
 125377 Link
ixekizumab Taltz Eli Lilly 3/22/2016 subcutaneous humanized
IL17A
Plaque psoriasis
 125521 Link
mepolizumab Nucala
GlaxoSmithKline
 11/4/2015 subcutaneous humanized IL5 Severe asthma 125526 Link
natalizumab Tysabri
Biogen Idec
 11/23/2004 intravenous humanized alpha-4 integrin Multiple sclerosis 125104 Link
necitumumab Portrazza Eli Lilly 11/24/2015 intravenous fully human EGFR Metastatic squamous
non-small cell lung carcinoma
 125547 Link
nivolumab Opdivo
Bristol-Myers Squibb
 12/22/2014 intravenous fully human
PD-1
Metastatic melanoma
 125554 Link
nivolumab Opdivo
Bristol-Myers Squibb
 3/4/2015 intravenous fully human
PD-1
 Metastatic squamous
non-small cell lung carcinoma
 125527 Link
obiltoxaximab Anthem Elusys Therapeutics 3/18/2016 intravenous chimeric Protective antigen of the Anthrax toxin
Inhalational anthrax
 125509 Link
obinutuzumab Gazyva Genentech 11/1/2013 intravenous humanized CD20 Chronic lymphocytic leukemia 125486 Link
ocrelizumab Ocrevus Genentech 3/28/2017 intravenous humanized CD20 Multiple sclerosis 761053 Link
ofatumumab Arzerra Glaxo Grp 10/26/2009 intravenous fully human CD20 Chronic lymphocytic leukemia 125326 Link
olaratumab Lartruvo Eli Lilly 10/19/2016 intravenous fully human
PDGFRA
Soft tissue sarcoma
 761038 Link
omalizumab Xolair Genentech 6/20/2003 subcutaneous humanized
IgE
 Moderate to severe persistent asthma 103976 Link
palivizumab Synagis MedImmune 6/19/1998 intramuscular humanized F protein of RSV Respiratory syncytial virus 103770 Link
panitumumab Vectibix Amgen 9/27/2006 intravenous fully human EGFR Metastatic colorectal cancer 125147 Link
pembrolizumab Keytruda Merck 9/4/2014 intravenous humanized
PD-1
Metastatic melanoma
 125514 Link
pertuzumab Perjeta Genentech 6/8/2012 intravenous humanized HER2 Metastatic breast cancer 125409 Link
ramucirumab Cyramza Eli Lilly 4/21/2014 intravenous fully human
VEGFR2
Gastric cancer
 125477 Link
ranibizumab Lucentis Genentech 6/30/2006 intravitreal injection humanized
VEGFR2
Wet age-related macular degeneration
 125156 Link
raxibacumab Raxibacumab Human Genome Sciences 12/24/2012 intravenous fully human Protective antigen of Bacillus anthracis
Inhalational anthrax
 125349 Link
reslizumab Cinqair
Teva
 3/23/2016 intravenous humanized IL5 Severe asthma 761033 Link
rituximab Rituxan Genentech 11/26/1997 intravenous chimeric CD20 B-cell
non-Hodgkin's lymphoma
 103705 Link
secukinumab Cosentyx Novartis 1/21/2015 subcutaneous fully human
IL17A
Plaque psoriasis
 125504 Link
siltuximab Sylvant
Janssen Biotech
 4/23/2014 intravenous chimeric IL6 Multicentric
Castleman's disease
 125496 Link
tocilizumab Actemra Genentech 1/8/2010 intravenous humanized
IL6R
 Rheumatoid arthritis 125276 Link
tocilizumab Actemra Genentech 10/21/2013 intravenous
subcutaneous		 humanized
IL6R
 Rheumatoid arthritis
Polyarticular juvenile idiopathic arthritis
Systemic juvenile idiopathic arthritis		 125472 Link
trastuzumab Herceptin Genentech 9/25/1998 intravenous humanized HER2 Metastatic breast cancer 103792 Link
ustekinumab Stelara
Centocor
 9/25/2009 subcutaneous fully human IL12
IL23
Plaque psoriasis
 125261 Link
ustekinumab Stelara
Janssen Biotech
 9/23/2016 subcutaneous
intravenous		 fully human IL12
IL23
Plaque psoriasis
Psoriatic arthritis
Crohn's disease
 761044 Link
vedolizumab Entyvio Takeda 5/20/2014 intravenous humanized integrin receptor Ulcerative colitis
Crohn's disease		 125476 Link
sarilumab Kevzara
Sanofi Aventis
 5/22/17 subcutaneous fully human
IL6R
 Rheumatoid arthritis 761037 Link
rituximab and hyaluronidase Rituxan Hycela Genentech 6/22/17 subcutaneous chimeric, co-formulated CD20 Follicular lymphoma
Diffuse large B-cell lymphoma
Chronic lymphocytic leukemia		 761064 Link
guselkumab Tremfya
Janssen Biotech
 7/13/17 subcutaneous fully human IL23
Plaque psoriasis
 761061 Link
inotuzumab ozogamicin Besponsa Wyeth 8/17/17 intravenous humanized,
antibody-drug conjugate
 CD22
Precursor B-cell acute lymphoblastic leukemia
 761040 Link
adalimumab-adbm
 Cyltezo Boehringer Ingelheim 8/25/17 subcutaneous fully human, biosimilar
TNF
Plaque psoriasis
 761058 Link
gemtuzumab ozogamicin Mylotarg Wyeth 9/1/17 intravenous humanized,
antibody-drug conjugate
 CD33 Acute myeloid leukemia 761060 Link
bevacizumab-awwb
 Mvasi Amgen 9/14/17 intravenous humanized, biosimilar
VEGF
 Metastatic
Non-small-cell lung carcinoma
Glioblastoma
Metastatic renal cell carcinoma
Cervical cancer
 761028 Link
benralizumab Fasenra AstraZeneca 11/14/17 subcutaneous humanized interleukin-5 receptor alpha subunit Severe asthma, eosinophilic phenotype 761070 Link
emicizumab-kxwh
 Hemlibra Genentech 11/16/17 subcutaneous humanized, bispecific Factor IXa, Factor X
Hemophilia A (congenital Factor VIII
deficiency) with Factor VIII inhibitors.		 761083 Link
trastuzumab-dkst
 Ogivri Mylan 12/1/17 intravenous humanized, biosimilar HER2 HER2-overexpressing breast cancer, metaststic gastric or gastroesophageal junction adenocarcinoma 761074 Link
infliximab-qbtx Ixifi Pfizer 12/13/17 intravenous chimeric, biosimilar
TNF
Plaque psoriasis
 761072 Link
ibalizumab-uiyk
 Trogarzo TaiMed Biologics 3/6/18 intravenous humanized CD4 HIV 761065 Link
tildrakizumab-asmn
 Ilumya Merck 3/20/18 subcutaneous humanized IL23
Plaque psoriasis
 761067 Link
burosumab-twza
 Crysvita Ultragenyx 4/17/18 subcutaneous fully human
FGF23
 X-linked hypophosphatemia 761068 Link
erenumab-aooe
 Aimovig Amgen 5/17/18 subcutaneous fully human
CGRP
receptor
Migraine headache
prevention		 761077 Link

Tositumomab – Bexxar – 2003 – CD20

Mogamulizumab – Poteligeo – August 2018 – CCR4

Moxetumomab pasudotox – Lumoxiti – September 2018 – CD22

PD-1

Polatuzumab vedotin – Polivy – June 2019 – CD79B

The

bispecific antibodies have yielded promising results in clinical trials. In April 2009, the bispecific antibody catumaxomab was approved in the European Union.[40][41]

Economics

Since 2000, the therapeutic market for monoclonal antibodies has grown exponentially. In 2006, the "big 5" therapeutic antibodies on the market were

autoimmune and inflammatory disorders, 'AIID') and rituximab (oncology and AIID) accounted for 80% of revenues in 2006. In 2007, eight of the 20 best-selling biotechnology drugs in the U.S. are therapeutic monoclonal antibodies.[42] This rapid growth in demand for monoclonal antibody production has been well accommodated by the industrialization of mAb manufacturing.[43]

References

  1. ^
    PMID 23370250
    .
  2. ISBN 978-0-8153-4101-7
    .
  3. ^
    ISBN 978-0-443-07310-6
    .
  4. ^
    PMID 18045976
    .
  5. S2CID 10169378
    .
  6. S2CID 43781004
    .
  7. S2CID 4161444
    .
  8. PMID 7427932
    .
  9. PMID 7032624
    .
  10. ^
    PMID 15780905
    .
  11. ^
    S2CID 19243664
    .
  12. PMID 1350088
    .
  13. S2CID 904440
    .
  14. S2CID 4241051
    .
  15. S2CID 9745527
    .
  16. PMID 20073133
    .
  17. PMID 20065651
    .
  18. S2CID 21298489
    .
  19. PMID 26784573
    .
  20. ^
    S2CID 4608450
    .
  21. PMID 28335888
    .
  22. ^
    ISBN 978-0-443-07145-4
    .
  23. ^
    S2CID 19375883
    .
  24. ^
    PMID 28967385
    .
  25. ^
    PMID 38219962
    .
  26. ^
    S2CID 26323381
    .
  27. PMID 28967385
    .
  28. ^ Goel, Ayush (20 August 2013). "Vasogenic cerebral oedema". radiopaedia.org. Retrieved 2017-11-01.
  29. ^
    PMID 21091109
    .
  30. PMID 37458272
    .
  31. PMID 27048170
    .
  32. S2CID 242999976
    .
  33. PMID 36449413
    .
  34. ^ "Leqembi | ALZFORUM". www.alzforum.org. Retrieved 2024-02-14.
  35. ^ Commissioner, Office of the (2023-07-07). "FDA Converts Novel Alzheimer's Disease Treatment to Traditional Approval". FDA. Retrieved 2024-02-14.
  36. PMID 12237768
    .
  37. PMID 15687597
    .
  38. S2CID 11603692
    .
  39. S2CID 25271222
    .
  40. PMID 20073127
    .
  41. PMID 20190561
    .
  42. PMID 20061824
    .
  43. PMID 20065641
    .

External links
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