anti-BCMA/alpha-amanitin antibody-drug conjugate HDP-101

An antibody-drug conjugate (ADC) consisting of a monoclonal antibody against the tumor-associated antigen (TAA) B-cell maturation antigen (BCMA, TNFRSF17) conjugated, via a cleavable linker, to the cytotoxic, RNA polymerase II inhibitor alpha-amanitin, with potential antineoplastic activity. Upon administration of anti-BCMA/alpha-amanitin ADC HDP-101, the antibody moiety targets and binds to the cell surface antigen BCMA expressed on certain cancer cells. Upon antibody/antigen binding, internalization and cleavage, the cytotoxic alpha-amanitin is released. Alpha-amanitin binds to and inhibits RNA polymerase II, prevents RNA synthesis, induces apoptosis, and inhibits the proliferation of BCMA-overexpressing tumor cells. BCMA, a receptor for a proliferation-inducing ligand (APRIL; tumor necrosis factor ligand superfamily member 13; TNFSF13), and B-cell activating factor (BAFF), is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a key role in plasma survival; it is found on the surfaces of plasma cells and is overexpressed on malignant plasma cells.