anti-HER2 antibody-drug conjugate FDA022-BB05

An antibody-drug conjugate (ADC) composed of trastuzumab, a monoclonal antibody directed against the tumor-associated antigen (TAA) human epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2), conjugated, via a valine-alanine (Val-Ala)-based cathepsin B-cleavable linker, to the cytotoxic DNA topoisomerase I inhibitor and exatecan derivative DXd (MAAA-1181a; MAAA-1181), with potential antineoplastic activity. Upon administration, anti-HER2 ADC FDA022-BB05 targets and binds to HER2 expressed on tumor cells. Upon binding, internalization, and linker cleavage, DXd is released. DXd inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of HER2-expressing tumor cells. FDA022-BB05 is also able to induce a bystander effect on neighboring cells in the tumor environment. This further inhibits the proliferation of tumor cells. HER2, a receptor tyrosine kinase that is mutated or overexpressed in many tumor cell types, plays an important role in tumor cell proliferation and tumor vascularization.