anti-EGFR/topoisomerase I inhibitor antibody-drug conjugate HLX42

An antibody-drug conjugate (ADC) composed of an immunoglobulin G1 (IgG1) monoclonal antibody directed against the tumor-associated antigen (TAA) epidermal growth factor receptor (EGFR) conjugated, via a cleavable linker, to a topoisomerase I inhibitor (TOP1i), with potential antineoplastic activity. Upon administration of anti-EGFR/TOP1i ADC HLX42, the anti-EGFR monoclonal antibody moiety targets and binds to EGFR expressed on tumor cells. Upon binding and cleavage in the tumor microenvironment (TME), the TOP1i moiety inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication which results in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of EGFR-expressing tumor cells. HLX42 also induces bystander killing activity. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.