Definition

An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the tumor-associated antigen (TAA) cadherin-6 (CDH6; CDH-6; K-cadherin) conjugated, via a protease cleavable linker, to the camptothecin analog and cytotoxic DNA topoisomerase I inhibitor exatecan, with potential antineoplastic activity. Upon administration of anti-CDH6/exatecan ADC CUSP06, the anti-CDH6 antibody moiety targets and binds to CDH6-expressing tumor cells. Upon uptake and cleavage of the linker by proteases, exatecan targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication and induction of apoptosis. This inhibits the proliferation of CDH6-expressing tumor cells. In addition, this may cause a bystander effect, thereby further killing CDH6-expressing tumor cells. CDH6, a member of the cadherin family and overexpressed by a variety of cancers, plays a key role in tumor cell proliferation.