Definition

An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), conjugated, via a cleavable linker, to a cytotoxic payload containing a camptothecin-based topoisomerase I (topo I) inhibitor, with potential antineoplastic activity. Upon administration of the anti-PD-L1 ADC HLX43, the anti-PD-L1 antibody moiety specifically targets and binds to PD-L1 expressed on tumor cells. The linker is specifically cleaved in the tumor microenvironment (TME), thereby delivering the toxin into PD-L1-expressing malignant cells, while sparing the normal cells. The cytotoxic agent specifically inhibits DNA topoisomerase I activity, causes double-strand breaks (DSBs) of DNA, and thereby inhibiting DNA replication and resulting in tumor cell apoptosis. This inhibits the proliferation of PD-L1-expressing tumor cells. In addition, HLX43 induces bystander killing effects, thereby further decreasing PD-L1-expessing tumor cells. PD-L1, a transmembrane protein, is expressed on the surface of certain immune cells and on many cancer cell types. PD-L1 binding to PD-1, a negative regulator of the immune system on activated T cells, limits the expansion and survival of CD8-positive T cells, suppresses the immune system and results in immune evasion.