anti-nectin-4 antibody-drug conjugate IPH4502

An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) Fc-competent monoclonal antibody directed against the cell surface adhesion molecule and tumor-associated antigen (TAA) nectin-4 (PVRL4) conjugated, via a hydrophilic cleavable linker, to the camptothecin analog and topoisomerase 1 inhibitor exatecan, with potential antineoplastic activity. Upon administration of anti-nectin-4 ADC IPH4502, the anti-nectin-4 antibody targets and binds to nectin-4 expressed on tumor cells. Upon binding, internalization and linker cleavage, exatecan is released. Exatecan inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of nectin-4-expressing tumor cells. IPH4502 is also able to induce a bystander effect on neighboring cells in the tumor environment. This further inhibits the proliferation of tumor cells. In addition, the Fc-competent monoclonal antibody of IPH4502 may induce both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against 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.