Biology:B-cell maturation antigen
Generic protein structure example
|BCMA TALL-1 binding domain|
crystal structure of stall-1 and bcma
|SCOP2||1oqd / SCOPe / SUPFAM|
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).
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).
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.
TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B. A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.
TNFRSF17 is implicated in leukemia, lymphomas, and multiple myeloma (see the "Mitelman Database"  and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,).
As a drug target
An antibody-drug conjugate Belantamab mafodotin (GSK2857916) has evaluated in patients with relapsed/refractory multiple myeloma. 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.
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.
ALLO-715 is a CAR-T therapy by Allogene Therapeutics that targets B-cell maturation antigen (BCMA). (As of June 2021), it is undergoing clinical trials for the treatment of multiple myeloma. On 21 April 2021, the FDA granted Regenerative Medicine Advanced Therapy status to ALLO-715. ALLO-715 is being investigated at Memorial Sloan Kettering Cancer Center and the Mayo Clinic as part of the UNIVERSAL trial for multiple myeloma, on its own and in conjunction with the selective gamma secretase inhibitor nirogacestat.
- ↑ "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): 3897–904. 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): 1147–54. 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): 9156–61. 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.
- ↑ "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.
- ↑ 14.0 14.1 Clinical trial number NCT04093596 for "Allogene Therapeutics" at ClinicalTrials.gov
- ↑ "FDA Grants RMAT Designation to ALLO-715 for Relapsed/Refractory Multiple Myeloma" (in en). 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.
- Human TNFRSF17 genome location and TNFRSF17 gene details page in the UCSC Genome Browser.
- "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): 284–9. 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): 1093–106. 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): 995–9. 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): 1322–30. 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): 9156–61. 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): 252–6. 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): 276–9. 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): 689–94. 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): 7218–27. 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): 3945–50. 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): 637–48. 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): 729–39. 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): 1179–83. 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.
Original source: https://en.wikipedia.org/wiki/B-cell maturation antigen. Read more