anti-nectin-4 antibody-drug conjugate LY4052031

An antibody-drug conjugate (ADC) composed of a human monoclonal antibody directed against the cell surface adhesion molecule and tumor-associated antigen (TAA) nectin-4 (PVRL4) conjugated, via a cleavable peptide linker, to the camptothecin analog and topoisomerase 1 inhibitor LSN3889710, with potential antineoplastic activity. Upon administration of the anti-nectin-4 ADC LY4052031, the anti-nectin-4 antibody moiety targets and binds to nectin-4 expressed on tumor cells. Upon binding, internalization and linker cleavage, LSN3889710 is released. LSN3889710 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. Nectin-4, an immunoglobulin-like protein belonging to the nectin family, is overexpressed in a variety of cancers.