B-cell maturation antigen
Template:Short description Template:Infobox gene Template:Short description
Script error: No such module "Infobox".Template:Template other 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] since June 2021[update]Template:Dated maintenance category (articles)Script error: No such module "Check for unknown parameters"., 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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- ↑ a b Clinical trial number NCT04093596 for "Allogene Therapeutics" at ClinicalTrials.gov
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External links
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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