Biology:B-cell maturation antigen
 Generic protein structure example |
| BCMA TALL-1 binding domain | |||||||||
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 crystal structure of stall-1 and bcma | |||||||||
| Identifiers | |||||||||
| Symbol | BCMA-Tall_bind | ||||||||
| Pfam | PF09257 | ||||||||
| InterPro | IPR015337 | ||||||||
| SCOP2 | 1oqd / SCOPe / SUPFAM | ||||||||
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B-cell maturation antigen (BCMA or BCM), also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 gene.
TNFRSF17 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF).[1][2][3]
Serum B-cell maturation antigen (sBCMA) is the cleaved form of BCMA, found at low levels in the serum of normal patients and generally elevated in patients with multiple myeloma (MM).[4]
Function
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation.[3]
Interactions
TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B.[5][6] A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.[5]
Clinical significance
TNFRSF17 is implicated in leukemia, lymphomas, and multiple myeloma[7] (see the "Mitelman Database" [8] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[9]).
As a drug target
An antibody-drug conjugate Belantamab mafodotin (GSK2857916) has evaluated in patients with relapsed/refractory multiple myeloma.[10] Belantamab mafodotin was approved in the United States in August 2020 for the treatment of patients with relapsed or refractory multiple myeloma who have received at least four prior therapies.[11]
Chimeric antigen receptor (CAR) T cells have emerged as an important therapy for multiple myeloma after first reports in preclinical and phase I clinical studies.[12] [13] A Phase 1b/2 study of JNJ-4528, a CAR-T cell therapy directed against BCMA in myeloma patients refractory to a proteasome inhibitor or immunomodulatory drug, and who had received an anti-CD38 antibody has been completed.[14]
ALLO-715 is a CAR-T therapy by Allogene Therapeutics that targets B-cell maturation antigen (BCMA).[15] (As of June 2021), it is undergoing clinical trials for the treatment of multiple myeloma.[16] On 21 April 2021, the FDA granted Regenerative Medicine Advanced Therapy status to ALLO-715.[17] ALLO-715 is being investigated at Memorial Sloan Kettering Cancer Center and the Mayo Clinic[18] as part of the UNIVERSAL trial for multiple myeloma, on its own and in conjunction with the selective gamma secretase inhibitor nirogacestat.[16][19]
References
- ↑ "A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma". The EMBO Journal 11 (11): 3897–3904. November 1992. doi:10.1002/j.1460-2075.1992.tb05482.x. PMID 1396583.
- ↑ "The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed". Nucleic Acids Research 22 (7): 1147–1154. April 1994. doi:10.1093/nar/22.7.1147. PMID 8165126.
- ↑ 3.0 3.1 "Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=608.
- ↑ "Serum B-Cell Maturation Antigen (BCMA) Levels Differentiate Primary Antibody Deficiencies". The Journal of Allergy and Clinical Immunology. In Practice 8 (1): 283–291.e1. January 2020. doi:10.1016/j.jaip.2019.08.012. PMID 31430592.
- ↑ 5.0 5.1 "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature 423 (6935): 49–56. May 2003. doi:10.1038/nature01543. PMID 12721620. Bibcode: 2003Natur.423...49L.
- ↑ "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1". Proceedings of the National Academy of Sciences of the United States of America 97 (16): 9156–9161. August 2000. doi:10.1073/pnas.160213497. PMID 10908663. Bibcode: 2000PNAS...97.9156S.
- ↑ "TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)". http://atlasgeneticsoncology.org/Genes/TNFRSF17ID42616ch16p13.html.
- ↑ "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer". http://cgap.nci.nih.gov/Chromosomes/Mitelman.
- ↑ "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org. http://Atlasgeneticsoncology.org.
- ↑ "Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study". The Lancet. Oncology 21 (2): 207–221. February 2020. doi:10.1016/s1470-2045(19)30788-0. PMID 31859245.
- ↑ "FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma". Clinical Cancer Research 28 (21): 4629–4633. November 2022. doi:10.1158/1078-0432.CCR-22-0618. PMID 35736811.
- ↑ "B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma". Clinical Cancer Research 19 (8): 2048–2060. April 2013. doi:10.1158/1078-0432.CCR-12-2422. PMID 23344265.
- ↑ "T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma". Blood 128 (13): 1688–1700. September 2016. doi:10.1182/blood-2016-04-711903. PMID 27412889.
- ↑ "Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM)" (in en). Blood 134 (Supplement_1): 577. 2019-11-13. doi:10.1182/blood-2019-121731. ISSN 0006-4971.
- ↑ "ALLO-715, an Allogeneic BCMA CAR T Therapy Possessing an Off-Switch for the Treatment of Multiple Myeloma". Blood 132 (Supplement 1): 591. 2018-11-29. doi:10.1182/blood-2018-99-119227. ISSN 0006-4971.
- ↑ 16.0 16.1 Clinical trial number NCT04093596 for "Allogene Therapeutics" at ClinicalTrials.gov
- ↑ "FDA Grants RMAT Designation to ALLO-715 for Relapsed/Refractory Multiple Myeloma" (in en). 21 April 2021. https://www.onclive.com/view/fda-grants-rmat-designation-to-allo-715-for-relapsed-refractory-multiple-myeloma.
- ↑ "Safety and Efficacy of ALLO-715 and ALLO-647 BCMA Allogenic CAR T Cells in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)" (in en). https://www.mayo.edu/research/clinical-trials/cls-20484366.
- ↑ "ASH: Allogene's off-the-shelf CAR-T posts 60% response rate in fiercely competitive BCMA field" (in en). 2020-12-07. https://www.fiercebiotech.com/biotech/ash-allogene-s-off-shelf-car-t-posts-60-response-rate-fiercely-competitive-bcma-field.
External links
- Human TNFRSF17 genome location and TNFRSF17 gene details page in the UCSC Genome Browser.
Further reading
- "BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells". Seminars in Immunology 18 (5): 297–304. October 2006. doi:10.1016/j.smim.2006.07.001. PMID 16919470.
- "The role of the BAFF/APRIL system on T cell function". Seminars in Immunology 18 (5): 284–289. October 2006. doi:10.1016/j.smim.2006.04.005. PMID 16931039.
- "BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes". International Immunology 7 (7): 1093–1106. July 1995. doi:10.1093/intimm/7.7.1093. PMID 8527407.
- "Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q". Genomics 60 (3): 295–308. September 1999. doi:10.1006/geno.1999.5927. PMID 10493829.
- "TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease". Nature 404 (6781): 995–999. April 2000. doi:10.1038/35010115. PMID 10801128. Bibcode: 2000Natur.404..995G.
- "TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase". Journal of Immunology 165 (3): 1322–1330. August 2000. doi:10.4049/jimmunol.165.3.1322. PMID 10903733.
- "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1". Proceedings of the National Academy of Sciences of the United States of America 97 (16): 9156–9161. August 2000. doi:10.1073/pnas.160213497. PMID 10908663. Bibcode: 2000PNAS...97.9156S.
- "APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity". Nature Immunology 1 (3): 252–256. September 2000. doi:10.1038/79802. PMID 10973284.
- "Presence of four major haplotypes in human BCMA gene: lack of association with systemic lupus erythematosus and rheumatoid arthritis". Genes and Immunity 2 (5): 276–279. August 2001. doi:10.1038/sj.gene.6363770. PMID 11528522.
- "Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival". Blood 103 (2): 689–694. January 2004. doi:10.1182/blood-2003-06-2043. PMID 14512299.
- "Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding". The Journal of Biological Chemistry 280 (8): 7218–7227. February 2005. doi:10.1074/jbc.M411714200. PMID 15542592.
- "Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor". Blood 105 (10): 3945–3950. May 2005. doi:10.1182/blood-2004-11-4463. PMID 15692072.
- "Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation". Cell Death and Differentiation 12 (6): 637–648. June 2005. doi:10.1038/sj.cdd.4401647. PMID 15846369.
- "Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL". Blood 109 (2): 729–739. January 2007. doi:10.1182/blood-2006-04-015958. PMID 16960154.
- "Identification of new splice variants of the genes BAFF and BCMA". Molecular Immunology 45 (4): 1179–1183. February 2008. doi:10.1016/j.molimm.2007.07.028. PMID 17825416.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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