TNFRSF17 Human

B-Cell Maturation Antigen (BCMA), also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17) or CD269, is a protein encoded by the TNFRSF17 gene. This receptor is predominantly expressed on the surface of mature B lymphocytes and plasma cells . BCMA plays a crucial role in B cell development and the autoimmune response by binding to the B-cell activating factor (BAFF), leading to the activation of NF-kappaB and MAPK8/JNK signaling pathways .

BCMA is specifically expressed in late-stage B cells and malignant plasma cells, particularly in multiple myeloma (MM) patients . The receptor’s expression is significantly higher in bone marrow mononuclear cells from MM patients compared to healthy donors . BCMA’s primary function is to regulate B cell proliferation and differentiation into antibody-secreting plasma cells. It achieves this by interacting with various members of the tumor necrosis factor (TNF) ligand superfamily, such as TNFSF13B (BAFF) .

BCMA has emerged as a promising therapeutic target for treating multiple myeloma. Several therapeutic strategies have been developed to target BCMA, including:

• Antibody-Drug Conjugates (ADCs): These are designed to deliver cytotoxic agents directly to BCMA-expressing cells .
• Bispecific T-cell Engagers (BiTEs): These antibodies bind to both BCMA and CD3ε on T-cells, facilitating T-cell recruitment and activation, leading to the lysis of target cells .
• Chimeric Antigen Receptor (CAR) T-Cells: Genetically engineered T-cells that recognize and kill BCMA-expressing cells .

BCMA can also be found in a soluble form (sBCMA) in the blood. Elevated levels of sBCMA are observed in MM patients with progressive disease, which may limit the efficacy of BCMA-targeted therapies . The use of γ-secretase inhibitors, which prevent the shedding of BCMA from plasma cells, has been proposed to enhance the effectiveness of these therapies .