anti-nectin-4/MMAE antibody-drug conjugate CRB-701

An antibody-drug conjugate (ADC) composed of an immunoglobulin G1 (IgG1) monoclonal antibody directed against the cell surface adhesion molecule and tumor-associated antigen (TAA) nectin-4 (PVRL4), site-specifically conjugated, via a cleavable linker, to the cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration of anti-nectin-4/MMAE ADC CRB-701, the anti-nectin-4 antibody moiety targets and binds to nectin-4 expressed on tumor cells. Upon binding, internalization, and linker cleavage, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces apoptosis in nectin-4-expressing tumor cells. Nectin-4, a TAA belonging to the nectin family, is overexpressed in a variety of cancers, but has a restricted distribution in normal tissue. CRB-701 may also induce anti-tumor activity through the induction of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against nectin-4-expressing tumor cells.