anti-HER3/topoisomerase I inhibitor antibody-drug conjugate DB-1310

An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against human epidermal growth factor receptor 3 (HER3; ErbB3) conjugated, via a maleimide tetrapeptide-based cleavable linker, to a cytotoxic DNA topoisomerase I inhibitor, with potential antineoplastic activity. Upon administration of anti-HER3 ADC DB-1310, the anti-HER3 antibody moiety targets and binds to HER3 expressed on tumor cells. Upon internalization, the topoisomerase I inhibitor targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA and resulting in DNA breaks, inhibition of DNA replication and apoptosis in HER3-expressing tumor cells. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors.