B-cell maturation antigen

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.

Interactions

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.

Clinical significance

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 been 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.

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. 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). , 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.

References

References

1. (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.
2. (April 1994). "The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed". Nucleic Acids Research.
3. "Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17".
4. (January 2020). "Serum B-Cell Maturation Antigen (BCMA) Levels Differentiate Primary Antibody Deficiencies". The Journal of Allergy and Clinical Immunology. In Practice.
5. (May 2003). "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature.
6. (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.
7. "TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)".
8. "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer".
9. "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org.
10. (February 2020). "Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study". The Lancet. Oncology.
11. (November 2022). "FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma". Clinical Cancer Research.
12. (April 2013). "B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma". Clinical Cancer Research.
13. (September 2016). "T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma". Blood.
14. (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.
15. (2018-11-29). "ALLO-715, an Allogeneic BCMA CAR T Therapy Possessing an Off-Switch for the Treatment of Multiple Myeloma". Blood.
16. (2021-06-23). "A Single-Arm, Open-Label, Phase 1 Study of the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-715 to Evaluate an Anti-BCMA Allogeneic CAR T Cell Therapy With or Without Nirogacestat in Subjects With Relapsed/Refractory Multiple Myeloma".
17. (21 April 2021). "FDA Grants RMAT Designation to ALLO-715 for Relapsed/Refractory Multiple Myeloma".
18. "Safety and Efficacy of ALLO-715 and ALLO-647 BCMA Allogenic CAR T Cells in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)".
19. (2020-12-07). "ASH: Allogene's off-the-shelf CAR-T posts 60% response rate in fiercely competitive BCMA field".