anti-c-Met antibody-drug conjugate YL211

An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the tumor-associated antigen (TAA) proto-oncogene c-Met (hepatocyte growth factor receptor; HGFR) site-specifically conjugated, via a tumor microenvironment (TME) activable protease-cleavable linker, to a topoisomerase 1 inhibitor (TOP1i), with potential antineoplastic activity. Upon administration of anti-c-Met ADC YL211, the anti-c-Met antibody moiety targets and binds to c-Met expressed on tumor cells. Upon proteolytic cleavage in the TME and the release of the topoisomerase I inhibitor, the topoisomerase I inhibitor targets and binds to DNA topoisomerase I, thereby inhibiting DNA replication and killing the c-Met-expressing cancer cells. In addition, YL211 is able to induce a bystander effect on neighboring cells. This further inhibits tumor cell proliferation. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis.