Anti-STEAP2/Exatecan Antibody-drug Conjugate AZD0516

**Semantic type:** Pharmacologic Substance

**Definition:** An antibody-drug conjugate (ADC) composed of a Fc-engineered monoclonal antibody targeting the tumor-associated antigen (TAA) six-transmembrane epithelial antigen of the prostate-2 (STEAP2; STEAP-2; STAMP1), linked via interchain cysteines to a maleimide-reactive, beta-glucuronidase-cleavable linker, to the cytotoxic agent and DNA topoisomerase I inhibitor (TOP1i) exatecan, with potential antineoplastic activity. Upon administration of anti-STEAP2/exatecan ADC AZD0516, the anti-STEAP2 antibody specifically targets and binds to STEAP2 expressed on tumor cells. Upon binding, internalization and linker cleavage, exatecan 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 STEAP2-expressing tumor cells. In addition, intracellular exatecan release may cause bystander cell killing, thereby further killing tumor cells. STEAP2 is a cell surface antigen overexpressed in prostate cancer with limited expression in normal tissue. The Fc domain of the antibody binder portion carries three amino acid point mutations to reduce unwanted Fc-mediated immune effector functions.

**Synonyms:** - ADC AZD0516 - AZD 0516 - AZD-0516 - AZD0516 - Anti-STEAP2 ADC AZD0516 - Anti-STEAP2 Antibody-drug Conjugate AZD0516 - Anti-STEAP2/Exatecan ADC AZD0516