anti-B7-H3 antibody-drug conjugate MGC026

An antibody-drug conjugate (ADC) composed of vobramitamab, a humanized monoclonal antibody directed against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276), site-specifically conjugated, via a cleavable glycan-based linker, to the camptothecin analog exatecan, with potential antineoplastic activity. Upon administration of anti-B7-H3 ADC MGC026, the anti-B7-H3 antibody moiety targets and binds to B7-H3-expressing tumor cells. Upon binding, internalization and linker cleavage, exatecan is released. Exatecan inhibits DNA topoisomerase I 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. MGC026 also induces bystander killing activity. 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 while its expression is limited on healthy cells. It is a negative regulator of T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis.