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CD20 (membrane-spanning 4-domains, subfamily A, member 1)

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2628

Nomenclature: CD20 (membrane-spanning 4-domains, subfamily A, member 1)

Family: CD molecules

Contents:

Gene and Protein Information Click here for help
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 Click here for help
B-lymphocyte antigen CD20 | MS4A2 | membrane-spanning 4-domains, subfamily A, member 1 | membrane-spanning 4-domains
Database Links Click here for help
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 go icon to follow link

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
ofatumumab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding 9.9 pKd 11
⤷ pKd 9.9 (Kd 1.21x10-10 M) [11]
Description: Binding affinity for clone 2F2 ((HuMax-CD20).
ocrelizumab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding 9.1 pKd 1
⤷ pKd 9.1 (Kd 8.4x10-10 M) [1]
rituximab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding 8.5 pKd 15
⤷ pKd 8.5 (Kd 3.1x10-9 M) [15]
veltuzumab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding 8.4 pKd 15
⤷ pKd 8.4 (Kd 3.6x10-9 M) [15]
BsAb (CD89-CD20) Peptide Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Binding 8.0 pKd 10
⤷ pKd 8.0 (Kd 9.37x10-9 M) [10]
Description: FACS analysis of antibody binding to CD20-expressing Raji cells.
glofitamab Peptide Approved drug Hs Binding 8.3 pEC50 4
⤷ pEC50 8.3 (EC50 4.8x10-9 M) [4]
Description: CD20 binding on primary human B cells
ibritumomab tiuxetan Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding - -
⤷
tositumomab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding - -
⤷
obinutuzumab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding - - 2,13
⤷ [2,13]
ublituximab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding - - 8
⤷ [8]
epcoritamab Peptide Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Binding - - 6
⤷ [6]
mosunetuzumab Peptide Approved drug Click here for species-specific activity table Hs Binding - - 16
⤷ [16]
odronextamab Peptide Hs Binding - - 14
⤷ [14]
divozilimab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs - - -
⤷
Antibody Comments
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.
Cell Type Associations
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  B cell (activation)
Immuno Process:  Immune system development
Immuno Process:  Cellular signalling
Immuno Disease Associations
Disease Name:  Pemphigus
Disease Synonyms:  no synonynms
Comment:  CD20 is the molecular target of the antibody veltuzumab.
Disease X-refs:  Disease Ontology: DOID:9182
References: 
Disease Name:  Relapsing-remitting multiple sclerosis
Disease Synonyms:  no synonynms
Comment:  CD20 is the molecular target of the RRMS therapeutic ocrelizumab.
Disease X-refs:  Disease Ontology: DOID:2378
References: 
Disease Name:  non-Hodgkin lymphoma
Disease Synonyms:  no synonynms
Comment:  CD20 is the molecular target of the B cell NHL therapeutic ibritumomab tiuxetan.
Disease X-refs:  Disease Ontology: DOID:0060060
OMIM: 605027
References: 
Disease Name:  Chronic lymphocytic leukemia
Disease Synonyms:  no synonynms
Comment:  CD20 is the molecular target of the CLL therapeutics ofatumumab and obinutuzumab.
Disease X-refs:  Disease Ontology: DOID:1040
OMIM: 151400
Orphanet: ORPHA67038
References: 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Common variable immunodeficiency
Description: CVID is a group of genetically heterogeneous primary immunodeficiencies. Whilst a small number of cases can be linked to deficiency in a single gene (see the OMIM links as examples), the cause is likely to be polygenic in the majority of cases. Symptoms vary between patients, but CVID is generally characterised by a failure to produce antibodies (hypogammaglobulinemia) and therefore susceptibility to recurrent infections and inflammation (including autoimmunity).
Disease Ontology: DOID:12177
OMIM: 613495, 607594, 606453, 240500, 613493
Orphanet: ORPHA1572
References:  7

References

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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]

How to cite this page

CD molecules: CD20 (membrane-spanning 4-domains, subfamily A, member 1). Last modified on 10/01/2024. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2628.