anti-B7-H3 antibody-drug conjugate DB-1311

An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) conjugated, via a cleavable linker, to the topoisomerase-1 inhibitor (TOP1i) P1021, with potential antineoplastic activity. Upon administration of anti-B7-H3 ADC DB-1311, the anti-B7-H3 antibody moiety targets and binds to B7-H3-expressing tumor cells. Upon binding, internalization and linker cleavage, P1021 is released, and inhibits DNA topoisomerase-1 activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell 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 is a negative regulator of T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis.