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CD37 molecule

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Target id: 3010

Nomenclature: CD37 molecule

Abbreviated Name: CD37

Family: CD molecules, Tetraspanins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 281 19q13.33 CD37 CD37 molecule 14
Mouse - 303 7 B3; Ch 7, 29.20 cM Cd37 CD37 antigen
Rat 4 281 1q22 Cd37 CD37 molecule
Gene and Protein Information Comments
The human CD37 gene produces two transcript variants and two protein isoforms: isoform A is 281 aa, isoform B is shorter at its N-terminus and is 213 aa. The longest mouse protein isoform (1) is 303 aa, isoform 2 is 278 aa, and isoform 3 is 281 aa.
Previous and Unofficial Names Click here for help
CD37 antigen | tetraspanin 26 | TSPAN26
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
lilotomab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding 8.6 pKd 3
pKd 8.6 (Kd 2.7x10-9 M) [3]
Description: Binding affinity to CD37 on Daudi (human Burkitt's lymphoma) cells.
naratuximab emtansine Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding 9.3 pEC50 5
pEC50 9.3 (EC50 5x10-10 M) [5]
Description: Binding affinity to CD37 antigen–positive cells as measured by flow cytometry.
otlertuzumab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding - - 10
[10]
Immunopharmacology Comments
CD37 is included in GtoImmuPdb as it is an immuno-oncology target that is being expoited for the development of novel therapeutics for the treatment of B cell malignancies, including non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) [5,9,12,15].
Cell Type Associations
Immuno Cell Type:  T cells
Comment:  CD37 expression by T cells and myeloid cells is lower than expression by mature B cells.
Immuno Cell Type:  B cells
Cell Ontology Term:   mature B cell (CL:0000785)
Comment:  CD37 is more highly expressed by mature B cells than by T cells or myeloid cells. It is not expressed by CD10+, CD34+ and CD34- B cell precursors in the bone marrow. Expression is lost in terminally differentiated plasma cells. CD37 is minimally detectable on T cells, monocytes and granulocytes, and is not expressed by natural killer (NK) cells, platelets or erythrocytes. CD37 is highly expressed by transformed mature B cell leukemia and lymphoma cells but not by myeloma cells.
References:  1,8,11
Physiological Consequences of Altering Gene Expression Click here for help
Cd37-deficiency in mice leads to spontaneous development of B cell lymphoma. Tumour development appears to be driven by constitutive activation of the IL-6 signaling pathway in a suppressor of cytokine signaling 3 (SOCS3)-dependent manner. Note that Cd37-negative mice show no overt changes in the development or cellular composition of lymphoid organs, despite the high level of Cd37 expression by cells of the immune system.
Species:  Mouse
Tissue: 
Technique: 
References:  4,6
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Diffuse large B-cell lymphoma
Description: DLBCL is an aggressive lymphoproliferative malignancy that arises in the lymph nodes. It is the most common subtype of non-Hodgkin lymphoma in adults. DLBCL is classified as a rare disease.
Synonyms: DLBCL
DLBL
Disease Ontology: DOID:0050745
Comments: 
Disease:  non-Hodgkin lymphoma
Description: A lymphoma that is characterized as any kind of lymphoma except Hodgkin's lymphoma.
Disease Ontology: DOID:0060060
OMIM: 605027
Comments: 
References:  15
General Comments
The CD37 protein has 4 hydrophobic transmembrane domains, and it belongs to the tetraspanin (TSPAN) protein family (HGNC family ID 768) [2,13]. It is expressed solely by cells of the immune system, and is involved in the regulation of immune responses [7], cell-cell interactions, cell development, activation, growth and motility [2,13]. CD37 is found on normal and malignant B cells. It has been identified as a tumour suppressor that protects against B cell lymphomagenesis, an effect that is mediated by inhibiting the IL-6 pathway [4], and in support of this mechanism is the observation that in human lymphomas CD37 deficiency is a marker of poor prognosis [16].

References

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1. Barrena S, Almeida J, Yunta M, López A, Fernández-Mosteirín N, Giralt M, Romero M, Perdiguer L, Delgado M, Orfao A et al.. (2005) Aberrant expression of tetraspanin molecules in B-cell chronic lymphoproliferative disorders and its correlation with normal B-cell maturation. Leukemia, 19 (8): 1376-83. [PMID:15931266]

2. Charrin S, le Naour F, Silvie O, Milhiet PE, Boucheix C, Rubinstein E. (2009) Lateral organization of membrane proteins: tetraspanins spin their web. Biochem. J., 420 (2): 133-54. [PMID:19426143]

3. Dahle J, Repetto-Llamazares AH, Mollatt CS, Melhus KB, Bruland OS, Kolstad A, Larsen RH. (2013) Evaluating antigen targeting and anti-tumor activity of a new anti-CD37 radioimmunoconjugate against non-Hodgkin's lymphoma. Anticancer Res., 33 (1): 85-95. [PMID:23267131]

4. de Winde CM, Veenbergen S, Young KH, Xu-Monette ZY, Wang XX, Xia Y, Jabbar KJ, van den Brand M, van der Schaaf A, Elfrink S et al.. (2016) Tetraspanin CD37 protects against the development of B cell lymphoma. J. Clin. Invest., 126 (2): 653-66. [PMID:26784544]

5. Deckert J, Park PU, Chicklas S, Yi Y, Li M, Lai KC, Mayo MF, Carrigan CN, Erickson HK, Pinkas J et al.. (2013) A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies. Blood, 122 (20): 3500-10. [PMID:24002446]

6. Knobeloch KP, Wright MD, Ochsenbein AF, Liesenfeld O, Löhler J, Zinkernagel RM, Horak I, Orinska Z. (2000) Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions. Mol. Cell. Biol., 20 (15): 5363-9. [PMID:10891477]

7. Levy S, Shoham T. (2005) The tetraspanin web modulates immune-signalling complexes. Nat. Rev. Immunol., 5 (2): 136-48. [PMID:15688041]

8. Link MP, Bindl J, Meeker TC, Carswell C, Doss CA, Warnke RA, Levy R. (1986) A unique antigen on mature B cells defined by a monoclonal antibody. J. Immunol., 137 (9): 3013-8. [PMID:3489782]

9. Pagel JM, Spurgeon SE, Byrd JC, Awan FT, Flinn IW, Lanasa MC, Eisenfeld AJ, Stromatt SC, Gopal AK. (2015) Otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR(™) therapeutic protein, for relapsed or refractory NHL patients. Br. J. Haematol., 168 (1): 38-45. [PMID:25146490]

10. Rafiq S, Siadak A, Butchar JP, Cheney C, Lozanski G, Jacob NK, Lapalombella R, McGourty J, Moledor M, Lowe R et al.. (2013) Glycovariant anti-CD37 monospecific protein therapeutic exhibits enhanced effector cell-mediated cytotoxicity against chronic and acute B cell malignancies. MAbs, 5 (5): 723-35. [PMID:23883821]

11. Schwartz-Albiez R, Dörken B, Hofmann W, Moldenhauer G. (1988) The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein. J. Immunol., 140 (3): 905-14. [PMID:3257508]

12. Stathis A, Flinn IW, Madan S, Maddocks K, Freedman A, Weitman S, Zucca E, Munteanu MC, Lia Palomba M. (2018) Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study. Invest New Drugs, 36 (5): 869-876. [PMID:29453628]

13. van Deventer SJ, Dunlock VE, van Spriel AB. (2017) Molecular interactions shaping the tetraspanin web. Biochem. Soc. Trans., 45 (3): 741-750. [PMID:28620035]

14. Virtaneva KI, Angelisová P, Baumruker T, Horejsí V, Nevanlinna H, Schröder J. (1993) The genes for CD37, CD53, and R2, all members of a novel gene family, are located on different chromosomes. Immunogenetics, 37 (6): 461-5. [PMID:8436422]

15. Witkowska M, Smolewski P, Robak T. (2018) Investigational therapies targeting CD37 for the treatment of B-cell lymphoid malignancies. Expert Opin Investig Drugs, 27 (2): 171-177. [PMID:29323537]

16. Xu-Monette ZY, Li L, Byrd JC, Jabbar KJ, Manyam GC, Maria de Winde C, van den Brand M, Tzankov A, Visco C, Wang J et al.. (2016) Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma. Blood, 128 (26): 3083-3100. [PMID:27760757]

How to cite this page

CD molecules: CD37 molecule. Last modified on 05/11/2020. Accessed on 24/11/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3010.