anti-nectin-4 antibody-drug conjugate LY4101174

An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) Fcg-silent monoclonal antibody directed against the cell surface adhesion molecule and tumor-associated antigen (TAA) nectin-4 (PVRL4) conjugated, via maleimide-beta-glucuronide poly-sarcosine linkers, to the camptothecin analog and topoisomerase 1 inhibitor exatecan, with potential antineoplastic activity. Upon administration of the anti-nectin-4 ADC LY4101174, the anti-nectin-4 antibody targets and binds to nectin-4 expressed on tumor cells. Upon binding and internalization, 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. Nectin-4, a TAA belonging to the nectin family, is overexpressed in a variety of cancers.