| Background | Belantamab mafodotin also known as GSK2857916 is a humanized, IgG1 antibody-drug conjugate (ADC) that binds specifically to BCMA. The parent anti-BCMA antibody (GSK2857914) is produced in an afucosylated form and is conjugated to the microtubule polymerization inhibitor MMAF, via a protease-resistant maleimidocaproyl (mc) linker, to produce the GSK2857916 ADC molecule. Upon binding to the cell surface, GSK2857916 is rapidly internalized and active cytotoxic drug (cys-mcMMAF) is released inside the cell causing cell-cycle arrest and apoptosis. Furthermore, the afucosylation of GSK2857916 leads to enhanced binding to FcγRIIIa receptors on the surface of immune effector cells, recruitment of immune cells, and antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP, respectively). This dual mechanism of action enables improved efficacy by targeting both dividing (via ADC) and non-dividing (via ADCC/ADCP) tumor cells. Recently, belantamab mafodotin was approved under the name BLENREP in the United States and European Union for the treatment of patients with relapsed or refractory multiple myeloma. |
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