TNFRSF17. also known as B-cell maturation antigen (BCMA), is a cell surface receptor belonging to the tumor necrosis factor receptor superfamily (TNFRSF). It plays a critical role in B-cell development, survival, and differentiation by binding to its ligands, APRIL (a proliferation-inducing ligand) and BAFF (B-cell activating factor). BCMA is predominantly expressed on plasma cells and mature B lymphocytes, making it a key biomarker for diseases involving plasma cell dysregulation, such as multiple myeloma (MM) and autoimmune disorders.
Antibodies targeting TNFRSF17 have garnered significant attention in therapeutic and diagnostic applications. In oncology, anti-BCMA antibodies are engineered as therapeutic agents, including antibody-drug conjugates (ADCs) and bispecific T-cell engagers (BiTEs), to direct immune cells or cytotoxic payloads toward malignant plasma cells. Notable examples include belantamab mafodotin (an ADC approved for relapsed/refractory MM) and teclistamab (a BiTE in clinical trials). Additionally, BCMA-targeting chimeric antigen receptor (CAR) T-cell therapies have shown remarkable efficacy in MM treatment.
Diagnostically, anti-TNFRSF17 antibodies are used to detect BCMA expression in tissues or serum, aiding in disease monitoring and prognosis. Research also explores their role in modulating immune responses in autoimmune conditions by interrupting BAFF/APRIL-BCMA signaling. Despite promising outcomes, challenges like on-target/off-tumor toxicity and resistance mechanisms remain areas of active investigation. Overall, TNFRSF17 antibodies represent a versatile tool bridging translational research and clinical innovation.