Category:Monoclonal antibodies

A monoclonal antibody (mAb) is a medicine consisting of an immunoglobulin protein produced by a single clone of B cells (or by recombinant expression of cloned B-cell genes) and engineered or selected to bind a defined molecular target with high affinity and specificity. The category sits within biologics and is, by both medicine count and clinical impact, the largest sub-category of biologic medicines, with more than a hundred approved products spanning every major therapeutic area: oncology, autoimmune disease, transplantation, infectious disease, allergic and atopic disease, neurology (multiple sclerosis, migraine, Alzheimer's), ophthalmology (age-related macular degeneration, diabetic retinopathy), haematology (paroxysmal nocturnal hemoglobinuria, haemophilia), and several rarer indications.

The history of the monoclonal antibody is a chapter of laboratory technique that opened the entire category. In August 1975 Georges Köhler and César Milstein at the MRC Laboratory of Molecular Biology in Cambridge published a 660-word paper in Nature describing the fusion of antibody-secreting mouse B cells with immortal myeloma cells to produce hybridomas that grew indefinitely and secreted a single antibody of defined specificity.^[1] Köhler and Milstein shared the 1984 Nobel Prize. The first therapeutic monoclonal antibody, muromonab-CD3 (OKT3), a murine anti-CD3 IgG2a used for prevention and treatment of acute kidney-transplant rejection, was approved in 1986. Its murine origin produced significant human-anti-mouse-antibody (HAMA) immunogenicity that limited repeat dosing and produced a substantial cytokine-release syndrome on first administration; the medicine has been retired in favour of less immunogenic alternatives.

The reduction of murine content in the monoclonal antibody was accomplished by three sequential engineering generations. The chimeric antibody (Reichmann and colleagues at the LMB, 1988), in which the murine variable regions are grafted onto human constant regions, reduced the foreign content from 100 percent to approximately 33 percent and the immunogenicity correspondingly; infliximab (Remicade, Centocor 1998 for Crohn's disease) and rituximab (Rituxan, Genentech/Biogen 1997 for non-Hodgkin lymphoma) are the most-prescribed chimerics. The humanised antibody (Greg Winter at the LMB, 1989), in which only the murine complementarity-determining regions are grafted onto a human framework, reduced foreign content to approximately 5-10 percent and produced a further reduction in immunogenicity; trastuzumab (Herceptin, Genentech 1998 for HER2-positive breast cancer) and daclizumab (Zenapax, Roche 1997 for transplant rejection) are early humanised examples. The fully human antibody, produced either by phage-display selection from human-antibody libraries or by transgenic mice carrying human immunoglobulin loci (the XenoMouse of Abgenix and the HuMab-Mouse of Medarex, both developed in the early 1990s), eliminated the foreign-origin component entirely; adalimumab (Humira, Abbott 2002) was the first phage-derived fully human therapeutic antibody and went on to become the best-selling medicine in the world for several years running.

The contemporary nomenclature reflects the engineering generation in the suffix of the international nonproprietary name. The standard four-letter stem is -mab for monoclonal antibody, preceded by a source-indicator letter: -o-mab for murine (muromonab, tositumomab), -xi-mab for chimeric (rituximab, infliximab, cetuximab), -zu-mab for humanised (trastuzumab, bevacizumab, pembrolizumab), -u-mab for fully human (adalimumab, nivolumab, denosumab), and additional infix letters that signal target system. The 2017 reform of the nomenclature (the World Health Organization International Nonproprietary Names review) is gradually retiring the source-of-origin infix in favour of the simpler -mab stem because the original distinction has lost clinical meaning (humanised and fully-human antibodies have similar immunogenicity in clinical practice).

The therapeutic applications now extend across essentially every domain of medicine. The oncologic monoclonal antibodies include the receptor-targeted (trastuzumab for HER2, cetuximab and panitumumab for EGFR, bevacizumab for VEGF, daratumumab for CD38, isatuximab for CD38, mogamulizumab for CCR4), the lymphocyte-depleting (rituximab for CD20, obinutuzumab and ofatumumab for CD20, alemtuzumab for CD52, blinatumomab as the CD3xCD19 bispecific T-cell engager), the immune-checkpoint inhibitors that have transformed oncology (ipilimumab anti-CTLA-4, the PD-1 antibodies pembrolizumab and nivolumab and dostarlimab, the PD-L1 antibodies atezolizumab and durvalumab and avelumab, the LAG-3 antibody relatlimab), and the antibody-drug conjugates (trastuzumab emtansine and trastuzumab deruxtecan for HER2-positive tumours, enfortumab vedotin for nectin-4, sacituzumab govitecan for TROP-2, polatuzumab vedotin for CD79b, brentuximab vedotin for CD30). The autoimmune-disease antibodies cover the TNF pathway (infliximab, adalimumab, golimumab, certolizumab pegol), IL-6 (tocilizumab, sarilumab), IL-1 (canakinumab), IL-17 (secukinumab, ixekizumab, brodalumab), IL-23 (ustekinumab, guselkumab, risankizumab, mirikizumab, tildrakizumab), IL-4 (dupilumab), IL-5 (mepolizumab, reslizumab, benralizumab), TSLP (tezepelumab), CD20 in multiple sclerosis (ocrelizumab, ofatumumab, ublituximab), the integrin antagonists (natalizumab, vedolizumab), C5 (eculizumab, ravulizumab, crovalimab), FcRn (efgartigimod, rozanolixizumab, batoclimab in trial), and the IgE antibody omalizumab. The ophthalmologic anti-VEGF antibodies (ranibizumab, brolucizumab, faricimab, the related VEGF-trap aflibercept) treat neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion. The neurology antibodies include the CGRP-pathway migraine prophylactics (erenumab, galcanezumab, fremanezumab, eptinezumab) and the anti-amyloid medicines for Alzheimer's disease (aducanumab, lecanemab, donanemab). The infectious-disease monoclonal antibodies include the RSV agents (palivizumab, nirsevimab), the SARS-CoV-2 monoclonals (now replaced as variants outpaced earlier products), the Ebola monoclonals (atoltivimab/maftivimab/odesivimab as Inmazeb, ansuvimab as Ebanga), and the rabies post-exposure monoclonals.

By therapeutic area:

• Oncology (cross-indexed under antineoplastics):
  • Receptor-targeted (HER2, EGFR, VEGF, etc.)
  • Lymphocyte-depleting (CD20, CD19, CD52)
  • Immune-checkpoint inhibitors (CTLA-4, PD-1, PD-L1, LAG-3)
  • Antibody-drug conjugates
  • Bispecific T-cell engagers (BiTE) and trispecifics
• Autoimmune and inflammatory disease (cross-indexed under anti-inflammatories, DMARDs, immunosuppressants, biologics):
  • TNF inhibitors
  • IL-6 and IL-1 antagonists
  • IL-17, IL-23, IL-4 axis
  • CD20 depletion (in MS and rheumatologic indications)
  • Integrin antagonists
  • Complement inhibitors
  • FcRn antagonists
  • Anti-IgE (omalizumab) for severe asthma
• Ophthalmology (intravitreal anti-VEGF): ranibizumab, brolucizumab, faricimab
• Neurology:
  • CGRP-pathway migraine prophylactics (cross-indexed under migraine prophylaxis)
  • Anti-amyloid for Alzheimer's: aducanumab (controversial), lecanemab, donanemab
  • Anti-CGRP in cluster headache
  • Anti-CD20 for multiple sclerosis (cross-indexed)
• Cardiovascular (cross-indexed under lipid-lowering agents):
  • PCSK9 inhibitors: alirocumab, evolocumab
  • Direct factor XI inhibitor abelacimab (in trial)
• Infectious disease (cross-indexed under antivirals / anti-infectives):
  • Respiratory syncytial virus: palivizumab, nirsevimab
  • Ebola: atoltivimab/maftivimab/odesivimab (Inmazeb), ansuvimab (Ebanga)
  • Rabies post-exposure: rabies immune globulin (polyclonal); rabies-specific monoclonals (Rabishield in India)
  • Anthrax: raxibacumab, obiltoxaximab (post-exposure)
  • C. difficile toxin B: bezlotoxumab
• Transplantation: basiliximab (IL-2 receptor antagonist), the polyclonal antithymocyte globulin (not strictly monoclonal), belatacept (fusion protein rather than monoclonal)
• Haematology and complement-mediated disease:
  • Anti-C5: eculizumab, ravulizumab (paroxysmal nocturnal hemoglobinuria, atypical HUS, generalised myasthenia gravis, neuromyelitis optica)
  • Emicizumab (FVIII mimetic, haemophilia A)
  • Caplacizumab (anti-von Willebrand factor, immune TTP)

The boundary of this category is "medicine consisting of a recombinant monoclonal antibody or a closely related antibody-derived molecule." The closely related antibody-drug conjugates (a monoclonal antibody linked to a cytotoxic payload through a cleavable linker) and the bispecific T-cell engagers (CD3-binding antibody linked to a tumour-antigen-binding domain) are included in this category by convention. The Fc-fusion proteins (etanercept, abatacept, belatacept, aflibercept) are not technically monoclonal antibodies but are listed under biologics alongside the mAbs. The intravenous immunoglobulin (polyclonal IgG from pooled human donors) is not a monoclonal antibody and is listed separately under immunomodulators. The CAR-T cell products and other cellular immunotherapies use engineered immunoglobulin-derived receptors but are not in themselves antibody medicines; they are listed under cellular medicines in biologics and immunomodulators.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.