Anti-Human BCMA (Belantamab) (IVMB0519)

B cell maturation antigen (BCMA, CD269, TNFRSF-17) is a type III transmembrane glycoprotein that is a member of the tumor necrosis factor (TNF) receptor superfamily¹. BCMA functions as a cell-surface receptor and is involved in the regulation of B cell proliferation, maturation, and differentiation into plasma cells, and is also required for the survival of long-lived plasma cells^{1, 2}. BCMA is more abundantly expressed on malignant plasma cells than normal plasma cells and is a novel treatment target for multiple myeloma (MM)^{1, 3, 4}, a plasma cell malignancy characterized by clonal proliferation of plasma cells within the bone marrow².

BCMA expression is upregulated during MM pathogenesis and evolution, with higher levels associated with poorer prognosis¹. The soluble form of BCMA, which is derived from direct shredding of membrane BMCA through γ-secretase activity, is also significantly elevated in MM patients relative to healthy individuals and is associated with worse clinical responses.

Belantamab (J6M0) is a novel afucosylated, humanized antagonistic anti-BCMA IgG1 monoclonal antibody⁴ produced in a Chinese Hamster Ovary cell line using recombinant DNA technology⁵. Belantamab has been used in clinical trials as part of the antibody conjugate belantamab mafodotin-blmf (GSK2857916)^{5, 6, 7} and has been shown to directly and indirectly target MM cells via multiple mechanisms of action⁴. Binding is BCMA-specific, with belantamab competing with BCMA’s two ligands BAFF and APRIL and also inhibiting ligand-induced NFκB signaling⁴. The afucosylation significantly increases the binding affinity of the Fc domain to the FcγR (FcγRIIIa) expressed on effector cells and enhances antibody-dependent cell-mediated cytotoxicity (ADCC)⁴.