Definition

An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) conjugated, via an enzymatically cleavable tetrapeptide-based linker, to the cytotoxic DNA topoisomerase I inhibitor and exatecan (DX-8951) derivative DXd (MAAA-1181a; MAAA-1181), with potential antineoplastic activity. Upon administration of the anti-B7-H3/DXd ADC DS-7300a, the anti-B7-H3 antibody targets and binds to B7-H3-expressing tumor cells. Upon cellular uptake and lysosomal degradation of the linker, DXd targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication and apoptosis. This inhibits the proliferation of B7-H3-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It plays a key role in tumor growth and immune responses. The ADC allows for reduced systemic exposure and enhanced delivery of the cytotoxic agent DXd.