Anti-Human BCMA (Belantamab) – Fc Muted™ (LT635-500ug)

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 cells1, 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, 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.