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Target has curated data in GtoImmuPdb
Target id: 2628
Nomenclature: CD20 (membrane-spanning 4-domains, subfamily A, member 1)
Family: CD molecules
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 4 | 297 | 11q12.2 | MS4A1 | membrane spanning 4-domains A1 | |
Mouse | 4 | 291 | 19 8.19 cM | Ms4a1 | membrane-spanning 4-domains, subfamily A, member 1 | |
Rat | - | 297 | 1q43 | Ms4a1 | membrane spanning 4-domains A1 |
Previous and Unofficial Names |
B-lymphocyte antigen CD20 | MS4A2 | membrane-spanning 4-domains, subfamily A, member 1 | membrane-spanning 4-domains |
Database Links | |
Alphafold | P11836 (Hs), P19437 (Mm) |
ChEMBL Target | CHEMBL2058 (Hs) |
DrugBank Target | P11836 (Hs) |
Ensembl Gene | ENSG00000156738 (Hs), ENSMUSG00000024673 (Mm), ENSRNOG00000020945 (Rn) |
Entrez Gene | 931 (Hs), 12482 (Mm), 309217 (Rn) |
Human Protein Atlas | ENSG00000156738 (Hs) |
KEGG Gene | hsa:931 (Hs), mmu:12482 (Mm), rno:309217 (Rn) |
OMIM | 112210 (Hs) |
Orphanet | ORPHA235193 (Hs) |
Pharos | P11836 (Hs) |
RefSeq Nucleotide | NM_152866 (Hs), NM_007641 (Mm), NM_001107578 (Rn) |
RefSeq Protein | NP_690605 (Hs), NP_031667 (Mm), NP_001101048 (Rn) |
UniProtKB | P11836 (Hs), P19437 (Mm) |
Wikipedia | MS4A1 (Hs) |
Download all structure-activity data for this target as a CSV file
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Ofatumumab, rituximab, tositumomab and ibritumomab tiuxetan are monoclonal antibodies against the CD20 molecule (MS4A1). These references contain some details of their use and function:- [3,9,12,18,20]. Although the KD value for ofatumumab is derived from [11], the originating patent is US8529902 [17]. A trifunctional monoclonal (Triomab®) called FBTA05, that targets CD20/CD3e was progressed to Phase 1/2 evaluation (NCT01138579), but recruitment was delayed and the trial terminated when FBTA05 became unavailable. See the entry for catumaxomab for full details of Triomab® mechanism of action. |
Immunopharmacology Comments |
CD20 is a B cell antigen, involved in B cell development and maturation to antibody-producing plasma cells [5]. CD20 has no known ligand and is suggested to act as a calcium channel. CD20 is the target of monoclonal antibodies approved for the treatment of B cell lymphomas and leukemias (rituximab, obinutuzumab, Ibritumomab tiuxetan, ofatumumab and tositumomab). In obese mice, anti-CD20 antibodies prevent insulin insensitivity and development of diabetes mellitus or metabolic syndrome [19], suggesting a potentially druggable autoimmune link between obesity, diabetes mellitus and metabolic syndrome. |
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||||
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1. Adams CW, Chan AC, Crowley CW, Lowman HB, Nakamura GR, Presta LG. (2004) Immunoglobulin variants and uses thereof. Patent number: WO2004056312. Assignee: Genentech, Inc.. Priority date: 16/12/2002. Publication date: 08/07/2004.
2. Alduaij W, Ivanov A, Honeychurch J, Cheadle EJ, Potluri S, Lim SH, Shimada K, Chan CH, Tutt A, Beers SA et al.. (2011) Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood, 117 (17): 4519-29. [PMID:21378274]
3. Anderson DR, Grillo-López A, Varns C, Chambers KS, Hanna N. (1997) Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma. Biochem Soc Trans, 25 (2): 705-8. [PMID:9191187]
4. Bacac M, Colombetti S, Herter S, Sam J, Perro M, Chen S, Bianchi R, Richard M, Schoenle A, Nicolini V et al.. (2018) CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies. Clin Cancer Res, 24 (19): 4785-4797. [PMID:29716920]
5. Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. (2005) The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun, 8: 140-74. [PMID:15564720]
6. Engelberts PJ, Hiemstra IH, de Jong B, Schuurhuis DH, Meesters J, Beltran Hernandez I, Oostindie SC, Neijssen J, van den Brink EN, Horbach GJ et al.. (2020) DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine, 52: 102625. [PMID:31981978]
7. Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IA, Dolman KM, Beaumont T, Tedder TF, van Noesel CJ, Eldering E et al.. (2010) CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest, 120 (1): 214-22. [PMID:20038800]
8. Le Garff-Tavernier M, Decocq J, de Romeuf C, Parizot C, Dutertre CA, Chapiro E, Davi F, Debré P, Prost JF, Teillaud JL et al.. (2011) Analysis of CD16+CD56dim NK cells from CLL patients: evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies. Leukemia, 25 (1): 101-9. [PMID:20975664]
9. Leandro MJ. (2013) B-cell subpopulations in humans and their differential susceptibility to depletion with anti-CD20 monoclonal antibodies. Arthritis Res Ther, 15 Suppl 1: S3. [PMID:23566754]
10. Li B, Xu L, Pi C, Yin Y, Xie K, Tao F, Li R, Gu H, Fang J. (2017) CD89-mediated recruitment of macrophages via a bispecific antibody enhances anti-tumor efficacy. Oncoimmunology, 7 (1): e1380142. [PMID:29296544]
11. Liu Q. (2013) Fully human antibodies against human cd20. Patent number: WO2013007052. Assignee: Qingfa Liu. Priority date: 13/07/2011. Publication date: 17/01/2013.
12. Mayes S, Brown N, Illidge TM. (2011) New antibody drug treatments for lymphoma. Expert Opin Biol Ther, 11 (5): 623-40. [PMID:21395497]
13. Reslan L, Dalle S, Herveau S, Perrial E, Dumontet C. (2014) Apoptotic induction by anti-CD20 antibodies in chronic lymphocytic leukemia: comparison of rituximab and obinutuzumab. Leuk Lymphoma, 55 (1): 188-90. [PMID:23537278]
14. Smith EJ, Olson K, Haber LJ, Varghese B, Duramad P, Tustian AD, Oyejide A, Kirshner JR, Canova L, Menon J et al.. (2015) A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys. Sci Rep, 5: 17943. [PMID:26659273]
15. Stein R, Qu Z, Chen S, Rosario A, Shi V, Hayes M, Horak ID, Hansen HJ, Goldenberg DM. (2004) Characterization of a new humanized anti-CD20 monoclonal antibody, IMMU-106, and Its use in combination with the humanized anti-CD22 antibody, epratuzumab, for the therapy of non-Hodgkin's lymphoma. Clin Cancer Res, 10 (8): 2868-78. [PMID:15102696]
16. Sun LL, Ellerman D, Mathieu M, Hristopoulos M, Chen X, Li Y, Yan X, Clark R, Reyes A, Stefanich E et al.. (2015) Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med, 7 (287): 287ra70. [PMID:25972002]
17. Teeling J, Ruuls S, Glennie M, van de Winkel JGJ, Parren P, Petersen J, Baadsgaard O, Huang H. (2013) for promoting proliferation and/or differentiation of B cells involved in cancers and autoimmune disorders; animal models; genetic engineering. Patent number: US8529902. Assignee: Genmab A/S. Priority date: 17/10/2002. Publication date: 10/09/2013.
18. White CA, Berlfein JR, Grillo-López AJ. (2000) Antibody-targeted immunotherapy for treatment of non-Hodgkin's lymphoma. Curr Pharm Biotechnol, 1 (4): 303-12. [PMID:11467328]
19. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN et al.. (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med, 17 (5): 610-7. [PMID:21499269]
20. Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S et al.. (1999) Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol, 17 (12): 3793-803. [PMID:10577851]
CD molecules: CD20 (membrane-spanning 4-domains, subfamily A, member 1). Last modified on 10/01/2024. Accessed on 14/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2628.