Definition

An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against the tumor-associated antigen (TAA) human epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2) conjugated, via a cleavable open-ring linker, to a topoisomerase I (TopoI) inhibitor-based payload, with potential antineoplastic activity. Upon administration of the anti-HER2/topoisomerase I inhibitor ADC GQ1005, the anti-HER2 monoclonal antibody moiety targets and binds to HER2 expressed on tumor cells. Upon cellular uptake, the TopoI inhibitor inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication which results in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of HER2-expressing tumor cells. Also, GQ1005 induces an additional bystander effect, thereby further killing tumor cells. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types.