Antibody targeting of B-cell maturation antigen on malignant plasma cells

摘要: B-cell maturation antigen (BCMA) is expressed on normal and malignant plasma cells represents a potential target for therapeutic intervention. BCMA binds to two ligands that promote tumor cell survival, proliferation inducing ligand (APRIL) activating factor. To selectively malignancies, we developed antibodies with blocking activity could cytotoxicity of multiple myeloma (MM) lines as naked or antibody-drug conjugates. We show SG1, an inhibitory antibody, blocks APRIL-dependent activation nuclear factor-kappaB in dose-dependent manner vitro. Cytotoxicity SG1 was assessed antibody after chimerization without Fc mutations enhance FcgammaRIIIA binding. The increased the antibody-dependent cell-mediated potency against MM by approximately 100-fold > = 2-fold increase maximal lysis. As alternative strategy, anti-BCMA were endowed direct cytotoxic conjugation drug, monomethyl auristatin F. most potent conjugate displayed IC(50) values < 130 pmol/L three different lines. Hence, both IgG drug conjugates warrant further evaluation candidates malignancies.