请输入您要查询的百科知识：

　

词条 Monoclonal antibody therapy
释义

  1. Antibody structure and function

  2. History

      Murine    Chimeric and humanized    Human monoclonal antibodies  

  3. Targeted conditions

     Cancer  Autoimmune diseases  Alzheimer's disease  Bapineuzumab  Solanezumab  Preventative trials 

  4. Therapy types

      Radioimmunotherapy    Antibody-directed enzyme prodrug therapy    Antibody-drug conjugates    Immunoliposome therapy    Checkpoint therapy  

  5. FDA-approved therapeutic antibodies

  6. Economics

  7. See also

  8. References

  9. External links

Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAb) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack those cells. Alternatively, in radioimmunotherapy a radioactive dose localizes a target cell line, delivering lethal chemical doses.[1] More recently antibodies have been used to bind to molecules involved in T-cell regulation to remove inhibitory pathways that block T-cell responses. This is known as immune checkpoint therapy.[2]

It is possible to create a mAb that is specific to almost any extracellular/cell surface target. Research and development is underway to create antibodies for diseases (such as rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Ebola[3] and different types of cancers).

Antibody structure and function

{{Further information|Monoclonal antibodies}}Immunoglobulin G (IgG) antibodies are large heterodimeric molecules, approximately 150 kDa and are composed of two kinds of polypeptide chain, called the heavy (~50kDa) and the light chain (~25kDa). The two types of light chains are kappa (κ) and lambda (λ). By cleavage with enzyme papain, the Fab (fragment-antigen binding) part can be separated from the Fc (fragment constant) 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.[4]Antibodies are a key component of the adaptive immune response, playing a central role in both in the recognition of foreign antigens and the stimulation of an immune response to them. The advent of monoclonal antibody technology has made it possible to raise antibodies against specific antigens presented on the surfaces of tumors.[5] Monoclonal antibodies can be acquired in the immune system via passive immunity or 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.[6] 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.[6]

Monoclonal antibody therapy may prove to be beneficial for cancer, 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.

History

Immunotherapy developed in the 1970s following the discovery of the structure of antibodies and the development of hybridoma technology, which provided the first reliable source of monoclonal antibodies.[8][9] These advances allowed for the specific targeting of tumors both in vitro and in vivo. Initial research on malignant neoplasms found mAb therapy of limited and generally short-lived success with blood malignancies.[10][11] Treatment also had to be tailored to each individual patient, which was impracticable in routine clinical settings.

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.

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.[12] Chimeric and humanized antibodies have generally replaced them in therapeutic antibody applications.[13] Understanding of proteomics has proven essential in identifying novel tumour targets.

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 cytotoxicity and the formation complexes after repeated administration, which resulted in mild allergic reactions and sometimes anaphylactic shock.[12] Hybridoma technology has been replaced by recombinant DNA technology, transgenic mice and phage display.[13]

Chimeric and humanized

To reduce murine antibody immunogenicity (attacks by the immune system against the antibody), murine molecules were engineered to remove immunogenic content and to increase immunologic efficiency.[12] This was initially achieved by the production of chimeric (suffix -ximab) and humanized antibodies (suffix -zumab). Chimeric antibodies are composed of murine variable regions fused onto human constant regions. Taking human gene sequences from the kappa light chain and the IgG1 heavy chain results in antibodies that are approximately 65% human. This reduces immunogenicity, and thus increases serum half-life.

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.[14][15] Increases in antibody-antigen binding strength have been achieved by introducing mutations into the complementarity determining regions (CDR),[16] using techniques such as chain-shuffling, randomization of complementarity-determining regions and antibodies with mutations within the variable regions induced by error-prone PCR, E. coli mutator strains and site-specific mutagenesis.[1]

Human monoclonal antibodies

Human monoclonal antibodies (suffix -umab) are produced using transgenic mice or phage display libraries by transferring human immunoglobulin genes into the murine genome and vaccinating the transgenic mouse against the desired antigen, leading to the production of appropriate monoclonal antibodies.[13] Murine antibodies in vitro are thereby transformed into fully human antibodies.[5]

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.[17][18]

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.[19]

Autoimmune diseases

Monoclonal antibodies used for autoimmune diseases include infliximab and adalimumab, which are effective in rheumatoid arthritis, Crohn's disease and ulcerative colitis by their ability to bind to and inhibit TNF-α.[20] Basiliximab and daclizumab inhibit IL-2 on activated T cells and thereby help preventing acute rejection of kidney transplants.[20] Omalizumab inhibits human immunoglobulin E (IgE) and is useful in moderate-to-severe allergic asthma.

Alzheimer's disease

Alzheimer’s disease (AD) is a multi-faceted, age-dependent, progressive neurodegenerative disorder, and is a major cause of dementia.[21] According to the Amyloid hypothesis, the accumulation of extracellular amyloid betapeptides (Aβ) into plaques via oligomerization leads to hallmark symptomatic conditions of AD through synaptic dysfunction and neurodegeneration.[22] Immunotherapy via exogenous monoclonal antibody (MAB) administration has been known to treat various central nervous disorders, such as AD, by inhibiting Aβ-oligomerization thereby preventing neurotoxicity. However, MABs are large for passive protein channels and are therefore inefficient due to the blood-brain barrier preventing MAB passage into the brain. However, the Peripheral Sink hypothesis proposes a mechanism where MABs may not need to cross the blood-brain barrier.[23] Therefore, many research studies are being conducted from failed attempts to treat AD in the past.[22]

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.[21] Vaccines can stimulate the immune system to produce its own antibodies,[24] in this case by introducing Aβ into transgenic animal models, known as active immunization. They can also introduce antibodies into animal models, known as passive immunization. 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.[22]. Therefore, several clinical trials using passive and active immunization approaches by development of certain drugs approved by the FDA are currently underway, and are expected to yield results in a couple of years.[22] The implementation of these drugs is during the onset of AD. Other research and drug development for early intervention and AD prevention is ongoing. Various drugs that are under research to treat AD include Bapineuzumab, Solanezumab, and Gautenerumab.

Bapineuzumab

Bapineuzumab, a humanized anti-aβ MAB, is directed against the N-terminus of Aβ. Phase II clinical trials of Bapineuzumab in mild to moderate AD patients resulted in reduced Aβ concentration in the brain. However, in patients with increased apolipoprotein (APOE) e4 carriers, Bapineuzumab treatment is also accompanied by vasogenic edema,[25] 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.[26]

In Phase III clinical trials, Bapineuzumab treatment is associated with reduced rate of accumulation of Aβ in the brain in APOE e4 patients, and no significant reduction of Aβ concentration in APOE e4 patients and non-APOE e4 patients. Therefore, Aβ plaque concentration were not reduced, and there is no significant clinical benefits in cognitive functioning. Bapineuzumab was discontinued after failing in Phase III clinical trial[26]

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 are currently ongoing.[23]

Preventative 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 preventative 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.[23]

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.[23]

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. Therefore, this preventing plaque formation and concentration without altering plasma concentration of the brain. Phase II and III clinical trials are currently being conducted.[23]

Therapy types

Radioimmunotherapy

Radioimmunotherapy (RIT) involves the use of radioactively-conjugated murine antibodies against cellular antigens. Most research involves their application to 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-Hodgkins lymphoma.

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.[27]

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.

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.[28]

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 CTLA-4 targeted by ipilimumab, PD-1 targeted by nivolumab and pembrolizumab and the tumor microenvironment.[2]

The tumor microenvironment (TME) features prevents the recruitment of T cells to the tumor. Ways include chemokine CCL2 nitration, which traps T cells in the stroma. Tumor vasculature helps tumors preferentially recruit other immune cells over T cells, in part through endothelial cell (EC)–specific expression of FasL, ETBR, and B7H3. Myelomonocytic and tumor cells can up-regulate expression of PD-L1, partly driven by hypoxic conditions and cytokine production, such as IFNβ. Aberrant metabolite production in the TME, such as the pathway regulation by IDO, can affect T cell functions directly and indirectly via cells such as Treg cells. CD8 cells can be suppressed by B cells regulation of TAM phenotypes. Cancer-associated fibroblasts (CAFs) have multiple TME functions, in part through extracellular matrix (ECM)–mediated T cell trapping and CXCL12-regulated T cell exclusion.[29]

FDA-approved therapeutic antibodies

{{Mainlist|List of monoclonal antibodies}}

The first FDA-approved therapeutic monoclonal antibody was a murine IgG2a CD3 specific transplant rejection drug, OKT3 (also called muromonab), in 1986. This drug found use in solid organ transplant recipients who became steroid resistant.[30] Hundreds of therapies are undergoing 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 [https://www.accessdata.fda.gov/drugsatfda_docs/label/1997/abcicen110597-lab.pdf Link]
adalimumab Humira Abbvie 12/31/2002 subcutaneous fully human TNF Rheumatoid arthritis 125057 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/adalabb123102LB.htm Link]
adalimumab-atto Amjevita Amgen 9/23/2016 subcutaneous fully human, biosimilar TNF Rheumatoid arthritis
Juvenile idiopathic arthritis
Psoriatic arthritis
Ankylosing spondylitis
Crohn's disease
Ulcerative colitis
Plaque psoriasis 		761024 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761024lbl.pdf Link]
ado-trastuzumab emtansine Kadcyla Genentech 2/22/2013 intravenous humanized, antibody-drug conjugate HER2 Metastatic breast cancer 125427 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125427lbl.pdf Link]
alemtuzumab Campath, Lemtrada Genzyme 5/7/2001 intravenous humanized CD52 B-cell chronic lymphocytic leukemia 103948 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/103948s5070lbl.pdf Link]
alirocumab Praluent Sanofi Aventis 7/24/2015 subcutaneous fully human PCSK9 Heterozygous familial hypercholesterolemia
Refractory hypercholesterolemia 		125559 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125559Orig1s000lbledt.pdf Link]
atezolizumab Tecentriq Genentech 5/18/2016 intravenous humanized PD-L1 Urothelial carcinoma 761034 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761034Orig1s000lbl.pdf Link]
atezolizumab Tecentriq Genentech 10/18/2016 intravenous humanized PD-L1 Urothelial carcinoma
Metastatic non-small cell lung cancer 		761041 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761041s000lbl.pdf Link]
avelumab Bavencio EMD Serono 3/23/2017 intravenous fully human PD-L1 Metastatic Merkel cell carcinoma 761049 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761049s000lbl.pdf Link]
basiliximab Simulect Novartis 5/12/1998 intravenous chimeric IL2RA Prophylaxis of acute organ rejection in renal transplant 103764 [https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/basnov051298lb.pdf Link]
belimumab Benlysta Human Genome Sciences 3/9/2011 intravenous fully human BLyS Systemic lupus erythematosus 125370 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125370s0000lbl.pdf Link]
bevacizumab Avastin Genentech 2/26/2004 intravenous humanized VEGF Metastatic colorectal cancer 125085 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/125085lbl.pdf Link]
bezlotoxumab Zinplava Merck 10/21/2016 intravenous fully human Clostridium difficile toxin B Prevent recurrence of Clostridium difficile infection 761046 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761046s000lbl.pdf Link]
blinatumomab Blincyto Amgen 12/3/2014 intravenous mouse, bispecific CD19 Precursor B-cell acute lymphoblastic leukemia 125557 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125557lbl.pdf Link]
brentuximab vedotin Adcetris Seattle Genetics 9/19/2011 intravenous chimeric, antibody-drug conjugate CD30 Hodgkin lymphoma
Anaplastic large-cell lymphoma 		125388 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125388s000,125399s000lbl.pdf Link]
brodalumab Siliq Valeant 2/15/2017 subcutaneous chimeric IL17RA Plaque psoriasis 761032 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761032lbl.pdf Link]
canakinumab Ilaris Novartis 6/17/2009 subcutaneous fully human IL1B Cryopyrin-associated periodic syndrome 125319 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125319s000lbl.pdf Link]
capromab pendetide ProstaScint Cytogen 10/28/1996 intravenous murine, radiolabeled PSMA Diagnostic imaging agent in newly diagnosed prostate cancer or post-prostatectomy 103608 [https://www.accessdata.fda.gov/drugsatfda_docs/label/1996/capcyt102896lab.pdf Link]
certolizumab pegol Cimzia UCB (company) 4/22/2008 subcutaneous humanized TNF Crohn's disease 125160 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/125160s000lbl.pdf Link]
cetuximab Erbitux ImClone Systems 2/12/2004 intravenous chimeric EGFR Metastatic colorectal carcinoma 125084 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/125084lbl.pdf Link]
daclizumab Zenapax Roche 12/10/1997 intravenous humanized IL2RA Prophylaxis of acute organ rejection in renal transplant 103749 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/daclhof072902lb.pdf Link]
daclizumab Zinbryta Biogen 5/27/2016 subcutaneous humanized IL2R Multiple sclerosis 761029 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761029s000lbl.pdf Link]
daratumumab Darzalex Janssen Biotech 11/16/2015 intravenous fully human CD38 Multiple myeloma 761036 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/761036Orig1s000lbledt.pdf Link]
denosumab Prolia, Xgeva Amgen 6/1/2010 subcutaneous fully human RANKL Postmenopausal women with osteoporosis 125320 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/125320s0000lbl.pdf Link]
dinutuximab Unituxin United Therapeutics 3/10/2015 intravenous chimeric GD2 Pediatric high-risk neuroblastoma 125516 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125516s000lbl.pdf Link]
dupilumab Dupixent Regeneron 3/28/2017 subcutaneous fully human IL4RA Atopic dermatitis 761055 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761055lbl.pdf Link]
durvalumab Imfinzi AstraZeneca 5/1/2017 intravenous fully human PD-L1 Urothelial carcinoma 761069 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761069s000lbl.pdf Link]
eculizumab Soliris Alexion 3/16/2007 intravenous humanized Complement component 5 Paroxysmal nocturnal hemoglobinuria 125166 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/125166lbl.pdf Link]
elotuzumab Empliciti Bristol-Myers Squibb 11/30/2015 intravenous humanized SLAMF7 Multiple myeloma 761035 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/761035s000lbl.pdf Link]
evolocumab Repatha Amgen 8/27/2015 subcutaneous fully human PCSK9 Heterozygous familial hypercholesterolemia
Refractory hypercholesterolemia 		125522 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125522s000lbl.pdf Link]
golimumab Simponi Centocor 4/24/2009 subcutaneous fully human TNF Rheumatoid arthritis
Psoriatic arthritis
Ankylosing spondylitis 		125289 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125289s000lbl.pdf Link]
golimumab Simponi Aria Janssen Biotech 7/18/2013 intravenous fully human TNF Rheumatoid arthritis 125433 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125433s000lbledt.pdf 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 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/ibriide021902LB.pdf Link]
idarucizumab Praxbind Boehringer Ingelheim 10/16/2015 intravenous humanized Fab dabigatran Emergency reversal of anticoagulant dabigatran 761025 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/761025lbl.pdf Link]
infliximab Remicade Centocor 8/24/1998 intravenous chimeric TNF alpha Crohn's disease 103772 [https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/inflcen082498lb.pdf Link]
infliximab-abda Renflexis Samsung Bioepis 4/21/2017 intravenous chimeric, biosimilar TNF Crohn's disease
Ulcerative colitis
Rheumatoid arthritis
Ankylosing spondylitis
Psoriatic arthritis
Plaque psoriasis 		761054 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761054Orig1s000lbledt.pdf Link]
infliximab-dyyb Inflectra Celltrion Healthcare 4/5/2016 intravenous chimeric, biosimilar TNF Crohn's disease
Ulcerative colitis
Rheumatoid arthritis
Ankylosing spondylitis
Psoriatic arthritis
Plaque psoriasis 		125544 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125544s000lbl.pdf Link]
ipilimumab Yervoy Bristol-Myers Squibb 3/25/2011 intravenous fully human CTLA-4 Metastatic melanoma 125377 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125377s0000lbl.pdf Link]
ixekizumab Taltz Eli Lilly 3/22/2016 subcutaneous humanized IL17A Plaque psoriasis 125521 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125521s000lbl.pdf Link]
mepolizumab Nucala GlaxoSmithKline 11/4/2015 subcutaneous humanized IL5 Severe asthma 125526 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125526Orig1s000Lbl.pdf Link]
natalizumab Tysabri Biogen Idec 11/23/2004 intravenous humanized alpha-4 integrin Multiple sclerosis 125104 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/125104lbl.pdf Link]
necitumumab Portrazza Eli Lilly 11/24/2015 intravenous fully human EGFR Metastatic squamous non-small cell lung carcinoma 125547 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125547s000lbl.pdf Link]
nivolumab Opdivo Bristol-Myers Squibb 12/22/2014 intravenous fully human PD-1 Metastatic melanoma 125554 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125554lbl.pdf Link]
nivolumab Opdivo Bristol-Myers Squibb 3/4/2015 intravenous fully human PD-1 Metastatic squamous non-small cell lung carcinoma 125527 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125527s000lbl.pdf Link]
obiltoxaximab Anthem Elusys Therapeutics 3/18/2016 intravenous chimeric Protective antigen of the Anthrax toxin Inhalational anthrax 125509 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125509lbl.pdf Link]
obinutuzumab Gazyva Genentech 11/1/2013 intravenous humanized CD20 Chronic lymphocytic leukemia 125486 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125486s000lbl.pdf Link]
ocrelizumab Ocrevus Genentech 3/28/2017 intravenous humanized CD20 Multiple sclerosis 761053 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761053lbl.pdf Link]
ofatumumab Arzerra Glaxo Grp 10/26/2009 intravenous fully human CD20 Chronic lymphocytic leukemia 125326 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125326lbl.pdf Link]
olaratumab Lartruvo Eli Lilly 10/19/2016 intravenous fully human PDGFRA Soft tissue sarcoma 761038 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761038lbl.pdf Link]
omalizumab Xolair Genentech 6/20/2003 subcutaneous humanized IgE Moderate to severe persistent asthma 103976 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/omalgen062003LB.pdf Link]
palivizumab Synagis MedImmune 6/19/1998 intramuscular humanized F protein of RSV Respiratory syncytial virus 103770 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/palimed102302LB.pdf Link]
panitumumab Vectibix Amgen 9/27/2006 intravenous fully human EGFR Metastatic colorectal cancer 125147 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/125147s0000lbl.pdf Link]
pembrolizumab Keytruda Merck 9/4/2014 intravenous humanized PD-1 Metastatic melanoma 125514 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125514lbl.pdf Link]
pertuzumab Perjeta Genentech 6/8/2012 intravenous humanized HER2 Metastatic breast cancer 125409 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125409lbl.pdf Link]
ramucirumab Cyramza Eli Lilly 4/21/2014 intravenous fully human VEGFR2 Gastric cancer 125477 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477lbl.pdf Link]
ranibizumab Lucentis Genentech 6/30/2006 intravitreal injection humanized VEGFR1
VEGFR2 		Wet age-related macular degeneration 125156 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/125156lbl.pdf Link]
raxibacumab Raxibacumab Human Genome Sciences 12/24/2012 intravenous fully human Protective antigen of Bacillus anthracis Inhalational anthrax 125349 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125349s000lbl.pdf Link]
reslizumab Cinqair Teva 3/23/2016 intravenous humanized IL5 Severe asthma 761033 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761033lbl.pdf Link]
rituximab Rituxan Genentech 11/26/1997 intravenous chimeric CD20 B-cell non-Hodgkin's lymphoma 103705 [https://www.accessdata.fda.gov/drugsatfda_docs/label/1997/ritugen112697-lab.pdf Link]
secukinumab Cosentyx Novartis 1/21/2015 subcutaneous fully human IL17A Plaque psoriasis 125504 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125504s000lbl.pdf Link]
siltuximab Sylvant Janssen Biotech 4/23/2014 intravenous chimeric IL6 Multicentric Castleman's disease 125496 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125496s000lbl.pdf Link]
tocilizumab Actemra Genentech 1/8/2010 intravenous humanized IL6R Rheumatoid arthritis 125276 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/125276lbl.pdf Link]
tocilizumab Actemra Genentech 10/21/2013 intravenous
subcutaneous 		humanized IL6R Rheumatoid arthritis
Polyarticular juvenile idiopathic arthritis
Systemic juvenile idiopathic arthritis 		125472 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125472s000lbl.pdf Link]
trastuzumab Herceptin Genentech 9/25/1998 intravenous humanized HER2 Metastatic breast cancer 103792 [https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/trasgen092598lb.pdf Link]
ustekinumab Stelara Centocor 9/25/2009 subcutaneous fully human IL12
IL23 		Plaque psoriasis 125261 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125261lbl.pdf Link]
ustekinumab Stelara Janssen Biotech 9/23/2016 subcutaneous
intravenous 		fully human IL12
IL23 		Plaque psoriasis
Psoriatic arthritis
Crohn's disease 		761044 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761044lbl.pdf Link]
vedolizumab Entyvio Takeda 5/20/2014 intravenous humanized integrin receptor Ulcerative colitis
Crohn's disease 		125476 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125476s000lbl.pdf Link]
sarilumab Kevzara Sanofi Aventis 5/22/17 subcutaneous fully human IL6R Rheumatoid arthritis 761037 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761037s000lbl.pdf 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 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761064s000lbl.pdf Link]
guselkumab Tremfya Janssen Biotech 7/13/17 subcutaneous fully human IL23 Plaque psoriasis 761061 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761061s000lbl.pdf Link]
inotuzumab ozogamicin Besponsa Wyeth 8/17/17 intravenous humanized, antibody-drug conjugate CD22 Precursor B-cell acute lymphoblastic leukemia 761040 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s000lbl.pdf Link]
adalimumab-adbm Cyltezo Boehringer Ingelheim 8/25/17 subcutaneous fully human, biosimilar TNF Rheumatoid arthritis
Juvenile idiopathic arthritis
Psoriatic arthritis
Ankylosing spondylitis
Crohn's disease
Ulcerative colitis
Plaque psoriasis 		761058 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761058lbl.pdf Link]
gemtuzumab ozogamicin Mylotarg Wyeth 9/1/17 intravenous humanized, antibody-drug conjugate CD33 Acute myeloid leukemia 761060 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761060lbl.pdf Link]
bevacizumab-awwb Mvasi Amgen 9/14/17 intravenous humanized, biosimilar VEGF Metastatic colorectal cancer
Non-squamous Non-small-cell lung carcinoma
Glioblastoma
Metastatic renal cell carcinoma
Cervical cancer 		761028 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761028s000lbl.pdf Link]
benralizumab Fasenra Astrazeneca 11/14/17 subcutaneous humanized interleukin-5 receptor alpha subunit Severe asthma, eosinophilic phenotype 761070 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf 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 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761083s000lbl.pdf Link]
trastuzumab-dkst Ogivri Mylan 12/1/17 intravenous humanized, biosimilar HER2 HER2-overexpressing breast cancer, metaststic gastric or gastroesophageal junction adenocarcinoma 761074 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761074s000lbl.pdf Link]
infliximab-qbtx Ixifi Pfizer 12/13/17 intravenous chimeric, biosimilar TNF Crohn's disease
Ulcerative colitis
Rheumatoid arthritis
Ankylosing spondylitis
Psoriatic arthritis
Plaque psoriasis 		761072 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761072s000lbl.pdf Link]
ibalizumab-uiyk Trogarzo TaiMed Biologics 3/6/18 intravenous humanized CD4 HIV 761065 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761065lbl.pdf Link]
tildrakizumab-asmn Ilumya Merck 3/20/18 subcutaneous humanized IL23 Plaque psoriasis 761067 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761067s000lbl.pdf Link]
burosumab-twza Crysvita Ultragenyx 4/17/18 subcutaneous fully human FGF23 X-linked hypophosphatemia 761068 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761068s000lbl.pdf Link]
erenumab-aooe Aimovig Amgen 5/17/18 subcutaneous fully human CGRP receptor Migraine headache prevention 761077 [https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761077s000lbl.pdf Link]

Recently, the bispecific antibodies, a novel class of therapeutic antibodies, have yielded promising results in clinical trials. In April 2009, the bispecific antibody catumaxomab was approved in the European Union.[31][32]

Economics

Since 2000, the therapeutic market for monoclonal antibodies has grown exponentially. In 2006, the “big 5” therapeutic antibodies on the market were bevacizumab, trastuzumab (both oncology), adalimumab, infliximab (both 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.[33] This rapid growth in demand for monoclonal antibody production has been well accommodated by the industrialization of mAb manufacturing.[34]

See also

  • Antigen 5T4
  • Immunotherapy
  • Immunoconjugate
  • Nomenclature of monoclonal antibodies
  • List of monoclonal antibodies, including investigational and withdrawn

References

1. ^1 {{cite journal | vauthors = Waldmann TA | title = Immunotherapy: past, present and future | journal = Nature Medicine | volume = 9 | issue = 3 | pages = 269–77 | date = March 2003 | pmid = 12612576 | doi = 10.1038/nm0303-269 | url = https://zenodo.org/record/1233435 }}
2. ^1 {{cite journal | vauthors = Sharma P, Allison JP | title = The future of immune checkpoint therapy | journal = Science | volume = 348 | issue = 6230 | pages = 56–61 | date = April 2015 | pmid = 25838373 | doi = 10.1126/science.aaa8172 | bibcode = 2015Sci...348...56S }}
3. ^{{cite journal | vauthors = Olinger GG, Pettitt J, Kim D, Working C, Bohorov O, Bratcher B, Hiatt E, Hume SD, Johnson AK, Morton J, Pauly M, Whaley KJ, Lear CM, Biggins JE, Scully C, Hensley L, Zeitlin L | title = Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 44 | pages = 18030–5 | date = October 2012 | pmid = 23071322 | pmc = 3497800 | doi = 10.1073/pnas.1213709109 | bibcode = 2012PNAS..10918030O }}
4. ^{{cite book | last = Janeway | first = Charles | authorlink = Charles Janeway |author2=Paul Travers |author3=Mark Walport |author4=Mark Shlomchik | title = Immunobiology; Fifth Edition | publisher = Garland Science | year = 2001 | location = New York and London| url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10| isbn = 978-0-8153-4101-7}}
5. ^1 {{cite book | author = Janeway CA, Jr. | title = Immunobiology | edition = 6th | publisher = Garland Science | year = 2005 | isbn = 978-0-443-07310-6|display-authors=etal}}
6. ^1 {{cite journal|last1=Baxter|first1=David|title=Active and passive immunity, vaccine types, excipients and licensing|journal=Occupational Medicine|date=December 2007|volume=57|issue=8|pages=552–6|doi=10.1093/occmed/kqm110|pmid=18045976}}
7. ^Modified from {{cite journal | vauthors = Carter P | title = Improving the efficacy of antibody-based cancer therapies | journal = Nature Reviews. Cancer | volume = 1 | issue = 2 | pages = 118–29 | date = November 2001 | pmid = 11905803 | doi = 10.1038/35101072 }}
8. ^{{cite journal|author=Prof FC Breedveld|author-link=Ferry Breedveld|title=Therapeutic monoclonal antibodies|journal=Lancet|year=2000|doi=10.1016/S0140-6736(00)01034-5|pmid=10703815|volume=355|issue=9205|pages=735–740}}
9. ^{{cite journal | vauthors = Köhler G, Milstein C | title = Continuous cultures of fused cells secreting antibody of predefined specificity | journal = Nature | volume = 256 | issue = 5517 | pages = 495–7 | date = August 1975 | pmid = 1172191 | doi = 10.1038/256495a0 | bibcode = 1975Natur.256..495K }}
10. ^{{cite journal | vauthors = Nadler LM, Stashenko P, Hardy R, Kaplan WD, Button LN, Kufe DW, Antman KH, Schlossman SF | title = Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen | journal = Cancer Research | volume = 40 | issue = 9 | pages = 3147–54 | date = September 1980 | pmid = 7427932 }}
11. ^{{cite journal | vauthors = Ritz J, Schlossman SF | title = Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma | journal = Blood | volume = 59 | issue = 1 | pages = 1–11 | date = January 1982 | pmid = 7032624 }}
12. ^1 2 {{cite journal | vauthors = Stern M, Herrmann R | title = Overview of monoclonal antibodies in cancer therapy: present and promise | journal = Critical Reviews in Oncology/Hematology | volume = 54 | issue = 1 | pages = 11–29 | date = April 2005 | pmid = 15780905 | doi = 10.1016/j.critrevonc.2004.10.011 }}
13. ^1 2 {{cite journal | vauthors = Hudson PJ, Souriau C | title = Engineered antibodies | journal = Nature Medicine | volume = 9 | issue = 1 | pages = 129–34 | date = January 2003 | pmid = 12514726 | doi = 10.1038/nm0103-129 }}
14. ^{{cite journal | vauthors = Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME, Shepard HM | title = Humanization of an anti-p185HER2 antibody for human cancer therapy | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 10 | pages = 4285–9 | date = May 1992 | pmid = 1350088 | pmc = 49066 | doi = 10.1073/pnas.89.10.4285 | bibcode = 1992PNAS...89.4285C }}
15. ^{{cite journal | vauthors = Presta LG, Lahr SJ, Shields RL, Porter JP, Gorman CM, Fendly BM, Jardieu PM | title = Humanization of an antibody directed against IgE | journal = Journal of Immunology | volume = 151 | issue = 5 | pages = 2623–32 | date = September 1993 | pmid = 8360482 }}
16. ^{{cite journal | vauthors = Chothia C, Lesk AM, Tramontano A, Levitt M, Smith-Gill SJ, Air G, Sheriff S, Padlan EA, Davies D, Tulip WR | title = Conformations of immunoglobulin hypervariable regions | journal = Nature | volume = 342 | issue = 6252 | pages = 877–83 | year = 1989 | pmid = 2687698 | doi = 10.1038/342877a0 | bibcode = 1989Natur.342..877C }}
17. ^{{cite journal | vauthors = Jefferis R, Lefranc MP | title = Human immunoglobulin allotypes: possible implications for immunogenicity | journal = mAbs | volume = 1 | issue = 4 | pages = 332–8 | date = July–August 2009 | pmid = 20073133 | pmc = 2726606 | doi = 10.4161/mabs.1.4.9122 }}
18. ^{{cite journal | vauthors = Chapman K, Pullen N, Coney L, Dempster M, Andrews L, Bajramovic J, Baldrick P, Buckley L, Jacobs A, Hale G, Green C, Ragan I, Robinson V | title = Preclinical development of monoclonal antibodies: considerations for the use of non-human primates | journal = mAbs | volume = 1 | issue = 5 | pages = 505–16 | year = 2009 | pmid = 20065651 | pmc = 2759500 | doi = 10.4161/mabs.1.5.9676 }}
19. ^{{cite journal | vauthors = Vennepureddy A, Singh P, Rastogi R, Atallah JP, Terjanian T | title = Evolution of ramucirumab in the treatment of cancer - A review of literature | journal = Journal of Oncology Pharmacy Practice | volume = 23 | issue = 7 | pages = 525–539 | date = June 2016 | pmid = 27306885 | doi = 10.1177/1078155216655474 }}
20. ^1 {{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |page=241 |isbn=978-0-443-07145-4 }}
21. ^1 {{cite journal|last1=Pul|first1=Refik|last2=Dodel|first2=Richard|last3=Stangel|first3=Martin|title=Antibody-based therapy in Alzheimer's disease|journal=Expert Opinion on Biological Therapy|date=March 2011|volume=11|issue=3|pages=343–357|doi=10.1517/14712598.2011.552884|pmid=21261567}}
22. ^1 2 3 {{cite journal|last1=van Dyck|first1=Christopher|authorlink1=Christopher H. van Dyck|title=Anti-Amyloid-β Monoclonal Antibodies for Alzheimer's Disease: Pitfalls and Promise|journal=Biological Psychiatry|volume=83|issue=4|pages=311–319|date=August 24, 2017|doi=10.1016/j.biopsych.2017.08.010|pmid=28967385|pmc=5767539}}
23. ^1 2 3 4 {{cite journal|last1=Panza|first1=F.|last2=Imbimbo|first2=B. P.|last3=Logroscino|first3=G.|title=Amyloid-directed monoclonal antibodies for the treatment of Alzheimer's disease: The point of no return?|journal=Expert Opinion on Biological Therapy|date=2014|volume=14|issue=10|pages=1465–76|doi=10.1517/14712598.2014.935332|pmid=24981190}}
24. ^{{cite journal|last1=Hanan|first1=Eilat|last2=Solomon|first2=Beka|title=Inhibitory effect of monoclonal antibodies on Alzheimer's P-amyloid peptide aggregation|journal=Amyloid|date=January 1996|volume=2|issue=3|pages=130–133|doi=10.3109/13506129609014365}}
25. ^{{cite web|last1=Goel|first1=Ayush|title=Vasogenic cerebral oedema|url=https://radiopaedia.org/articles/vasogenic-cerebral-oedema|website=radiopaedia.org|accessdate=2017-11-01|language=en}}
26. ^1 {{cite journal|last1=Panza|first1=F.|last2=Imbimbo|first2=B.P.|last3=D'aOnofrio|first3=G.|last4=Pietrarossa|first4=G.|last5=Seripa|first5=Davide|last6=Frisardi|first6=V.|title=Bapineuzumab: anti-β-amyloid monoclonal antibodies for the treatment of Alzheimer's disease|journal=V.|date=November 2010|volume=2|issue=6|pages=767–82|doi=10.2217/imt.10.80|pmid=21091109}}
27. ^{{cite journal | vauthors = Francis RJ, Sharma SK, Springer C, Green AJ, Hope-Stone LD, Sena L, Martin J, Adamson KL, Robbins A, Gumbrell L, O'Malley D, Tsiompanou E, Shahbakhti H, Webley S, Hochhauser D, Hilson AJ, Blakey D, Begent RH | title = A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours | journal = British Journal of Cancer | volume = 87 | issue = 6 | pages = 600–7 | date = September 2002 | pmid = 12237768 | pmc = 2364249 | doi = 10.1038/sj.bjc.6600517 }}
28. ^{{cite journal | vauthors = Krauss WC, Park JW, Kirpotin DB, Hong K, Benz CC | title = Emerging antibody-based HER2 (ErbB-2/neu) therapeutics | journal = Breast Disease | volume = 11 | pages = 113–24 | year = 2000 | pmid = 15687597 | doi=10.3233/bd-1999-11110}}
29. ^{{cite journal | vauthors = Joyce JA, Fearon DT | title = T cell exclusion, immune privilege, and the tumor microenvironment | journal = Science | volume = 348 | issue = 6230 | pages = 74–80 | date = April 2015 | pmid = 25838376 | doi = 10.1126/science.aaa6204 | bibcode = 2015Sci...348...74J }}
30. ^{{cite journal | vauthors = Hooks MA, Wade CS, Millikan WJ | title = Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation | journal = Pharmacotherapy | volume = 11 | issue = 1 | pages = 26–37 | year = 1991 | pmid = 1902291 | doi = 10.1002/j.1875-9114.1991.tb03595.x | doi-broken-date = 2019-03-03 }}
31. ^{{cite journal | vauthors = Chames P, Baty D | title = Bispecific antibodies for cancer therapy: the light at the end of the tunnel? | journal = mAbs | volume = 1 | issue = 6 | pages = 539–47 | year = 2009 | pmid = 20073127 | pmc = 2791310 | doi = 10.4161/mabs.1.6.10015 }}
32. ^{{cite journal|last=Linke|first=Rolf |author2=Klein, Anke |author3=Seimetz, Diane|title=Catumaxomab: Clinical development and future directions|journal=mAbs|year=2010|volume=2|issue=2|pages=129–136|doi=10.4161/mabs.2.2.11221|pmid=20190561 |url=http://www.landesbioscience.com/journals/mabs/article/11221/ |pmc=2840231}}
33. ^{{cite journal | vauthors = Scolnik PA | title = mAbs: a business perspective | journal = mAbs | volume = 1 | issue = 2 | pages = 179–84 | year = 2009 | pmid = 20061824 | pmc = 2725420 | doi = 10.4161/mabs.1.2.7736 }}
34. ^{{cite journal | vauthors = Kelley B | title = Industrialization of mAb production technology: the bioprocessing industry at a crossroads | journal = mAbs | volume = 1 | issue = 5 | pages = 443–52 | year = 2009 | pmid = 20065641 | pmc = 2759494 | doi = 10.4161/mabs.1.5.9448 }}

External links

  • Cancer Management Handbook: Principles of Oncologic Pharmacotherapy {{Registration required}}
{{Extracellular chemotherapeutic agents}}{{DEFAULTSORT:Monoclonal Antibody Therapy}}Biološka zdravila

4 : Immunology|Monoclonal antibodies for tumors|Monoclonal antibodies|Antivirals
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/11 13:36:44