B-cell maturation antigen

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).
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 - Related Diseases.
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 GSK2857916 (belantamab mafodotin) demonstrated activity in patients with relapsed/refractory multiple myeloma, previously treated with an immunomodulatory drug, proteosome inhibitor, or who were intolerant/refractory to an anti-CD38 monoclonal antibody. The primary toxicities were keratopathy, thrombocytopenia, and anemia.
Belantamab mafodotin (GSK2857916) was approved for medical use in the United States in August 2020.
A Phase 1b/2 study of 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 showed a 91% overall response rate. Main toxicities were cytokine release syndrome and cytopenias.