DS-7300a, a novel B7-H3-targeting antibody-drug conjugate with a novel DNA topoisomerase I inhibitor DXd, exhibits potent anti-tumor effects in nonclinical models

Background: B7-H3 (CD276) is a type I transmembrane protein belonging to the B7 family which includes immune checkpoint molecules such as CTLA-4 ligands and PD-L1. B7-H3 is highly expressed in various types of solid tumors with low expression in normal tissues. Several studies have reported that B7-H3 overexpression is associated with poor prognosis in several types of cancers. These findings support B7-H3 as an attractive molecular target for anti-cancer therapies. We generated DS-7300a, a B7-H3-targeting antibody-drug conjugate (ADC), which is composed of a humanized anti-B7-H3 monoclonal antibody, an enzymatically cleavable peptide-based linker, and a novel exatecan derivative (DXd) that is a potent DNA topoisomerase I inhibitor.