Tumor necrosis factor receptor superfamily member 17 (TNFRSF17) (TNFRSF17)

Tumor necrosis factor receptor superfamily member 17 (TNFRSF17), commonly known as B-cell maturation antigen (BCMA), is a cell surface receptor essential for the survival of long-lived plasma cells [1, 3]. It is characterized by a highly restricted expression pattern, found almost exclusively on mature B-lineage cells, such as plasmablasts and plasma cells, and is notably absent from hematopoietic stem cells and naive B cells [3, 9]. The receptor functions by binding to its primary ligands, BAFF and APRIL, which activates downstream signaling cascades including the NF-kappaB and JNK pathways to promote cell proliferation and prevent apoptosis [2, 12]. In the context of disease, BCMA is significantly overexpressed on the surface of malignant plasma cells in nearly all patients with multiple myeloma, making it an ideal target for immunotherapy [1, 4]. Therapeutic interventions targeting BCMA include chimeric antigen receptor (CAR) T-cell therapies, bispecific T-cell engagers, and antibody-drug conjugates, which have revolutionized the treatment of relapsed or refractory multiple myeloma [4, 6]. Soluble BCMA, which is shed from the cell surface by gamma-secretase, serves as a valuable biomarker for monitoring disease burden and predicting patient outcomes [12, 16]. However, the use of BCMA-targeted agents is associated with specific safety concerns, such as cytokine release syndrome, neurotoxicity, and the risk of infections due to the depletion of normal plasma cells [4, 6]. Resistance to these therapies can also emerge through mechanisms like biallelic deletion of the TNFRSF17 gene or antigen escape, necessitating ongoing research into multi-targeted approaches [6, 8].

Other names

B-cell maturation antigenBCMACD269B-cell maturation proteinBCMTumor necrosis factor receptor superfamily member 17

Chimeric antigen receptor T-cell therapy, bispecific T-cell engager, and antibody-drug conjugate targeting BCMA-expressing cells to induce cytotoxicity and redirect T-cell activity.