anti-B7-H3 antibody-drug conjugate MHB088C

An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) conjugated to an as of yet undisclosed topoisomerase-1 inhibitor via a cleavable linker, with potential antineoplastic activity. Upon administration of anti-B7-H3 ADC MHB088C, the antibody moiety targets and binds to B7-H3-expressing tumor cells. Upon binding, internalization and linker cleavage, the topoisomerase-1 inhibitor is released and inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and apoptosis in tumor cells expressing B7-H3. 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.