Definition

An antibody-drug conjugate (ADC) composed of the bispecific monoclonal antibody anbenitamab, directed against two distinct epitopes of the extracellular dimerization domain of the tumor-associated antigen (TAA) human tyrosine kinase receptor epidermal growth factor receptor 2 (HER2; ErbB2; HER-2), site-specifically conjugated via N glycosylation site to a topoisomerase-1 inhibitor, with potential antineoplastic activity. Upon administration of anti-HER2 ADC JSKN003, the anbenitamab moiety simultaneously targets and binds to two separate, non-overlapping epitopes of HER2 expressed on tumor cells. Upon binding and internalization, the topoisomerase-1 inhibitor moiety is released, binds to topoisomerase-1 and stabilizes cleaved DNA-topoisomerase-1 complexes. This prevents DNA re-ligation, induces irreversible DNA strand breaks, prevents DNA repair, and leads to cycle arrest and apoptosis specifically in tumor cells expressing HER2. HER2, a receptor tyrosine kinase that is mutated or overexpressed in many tumor cell types, plays an important role in tumor cell proliferation and tumor vascularization.