B-cell maturation antigen

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BCMA TALL-1 binding domain
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crystal structure of stall-1 and bcma
Identifiers
SymbolBCMA-Tall_bind
PfamPF09257
InterProIPR015337
SCOP21oqd / SCOPe / SUPFAM
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Available protein structures:
PDB  IPR015337 PF09257 (ECOD; PDBsum)  
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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 been 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

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  1. ^ Page Module:Citation/CS1/styles.css has no content.Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A (November 1992). "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. doi:10.1002/j.1460-2075.1992.tb05482.x. PMC 556899. PMID 1396583.
  2. ^ Page Module:Citation/CS1/styles.css has no content.Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A (April 1994). "The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed". Nucleic Acids Research. 22 (7): 1147–1154. doi:10.1093/nar/22.7.1147. PMC 523635. PMID 8165126.
  3. ^ a b Page Module:Citation/CS1/styles.css has no content."Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17".
  4. ^ Page Module:Citation/CS1/styles.css has no content.Maglione PJ, Ko HM, Tokuyama M, Gyimesi G, Soof C, Li M, et al. (January 2020). "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. doi:10.1016/j.jaip.2019.08.012. PMC 6980522. PMID 31430592.
  5. ^ a b Page Module:Citation/CS1/styles.css has no content.Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, et al. (May 2003). "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature. 423 (6935): 49–56. Bibcode:2003Natur.423...49L. doi:10.1038/nature01543. PMID 12721620. S2CID 4373708.
  6. ^ Page Module:Citation/CS1/styles.css has no content.Shu HB, Johnson H (August 2000). "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. Bibcode:2000PNAS...97.9156S. doi:10.1073/pnas.160213497. PMC 16838. PMID 10908663.
  7. ^ Page Module:Citation/CS1/styles.css has no content."TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)". atlasgeneticsoncology.org.
  8. ^ Page Module:Citation/CS1/styles.css has no content."Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer". Archived from the original on 2016-05-25. Retrieved 2015-01-29.
  9. ^ Page Module:Citation/CS1/styles.css has no content."Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org.
  10. ^ Page Module:Citation/CS1/styles.css has no content.Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. (February 2020). "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. doi:10.1016/s1470-2045(19)30788-0. PMID 31859245. S2CID 209425201.
  11. ^ Page Module:Citation/CS1/styles.css has no content.Baines AC, Ershler R, Kanapuru B, Xu Q, Shen G, Li L, et al. (November 2022). "FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma". Clinical Cancer Research. 28 (21): 4629–4633. doi:10.1158/1078-0432.CCR-22-0618. PMC 9633344. PMID 35736811.
  12. ^ Page Module:Citation/CS1/styles.css has no content.Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. (April 2013). "B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma". Clinical Cancer Research. 19 (8): 2048–2060. doi:10.1158/1078-0432.CCR-12-2422. PMC 3630268. PMID 23344265.
  13. ^ Page Module:Citation/CS1/styles.css has no content.Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, et al. (September 2016). "T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma". Blood. 128 (13): 1688–1700. doi:10.1182/blood-2016-04-711903. PMC 5043125. PMID 27412889.
  14. ^ Page Module:Citation/CS1/styles.css has no content.Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, et al. (2019-11-13). "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)". Blood. 134 (Supplement_1): 577. doi:10.1182/blood-2019-121731. ISSN 0006-4971. S2CID 209265279.
  15. ^ Page Module:Citation/CS1/styles.css has no content.Sommer C, Boldajipour B, Valton J, Galetto R, Bentley T, Sutton J, Ni Y, Leonard M, Van Blarcom T, Smith J, Chaparro-Riggers J (2018-11-29). "ALLO-715, an Allogeneic BCMA CAR T Therapy Possessing an Off-Switch for the Treatment of Multiple Myeloma". Blood. 132 (Supplement 1): 591. doi:10.1182/blood-2018-99-119227. ISSN 0006-4971.
  16. ^ a b Clinical trial number NCT04093596 for "Allogene Therapeutics" at ClinicalTrials.gov
  17. ^ Page Module:Citation/CS1/styles.css has no content."FDA Grants RMAT Designation to ALLO-715 for Relapsed/Refractory Multiple Myeloma". OncLive. 21 April 2021. Retrieved 2022-05-10.
  18. ^ Page Module:Citation/CS1/styles.css has no content."Safety and Efficacy of ALLO-715 and ALLO-647 BCMA Allogenic CAR T Cells in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)". Mayo Clinic. Retrieved 2022-05-10.
  19. ^ Page Module:Citation/CS1/styles.css has no content.Taylor NP (2020-12-07). "ASH: Allogene's off-the-shelf CAR-T posts 60% response rate in fiercely competitive BCMA field". Fierce Biotech. Retrieved 2022-05-10.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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