zaptuzumab

Zaptuzumab is a monoclonal antibody that targets death receptor 5 (DR5), also known as tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2). Developed by Mabplex, it serves as the targeting component for antibody-drug conjugates (ADCs) such as Oba01 (zaptuzumab-PY-VC-MMAE) and Zapadcine-1 (zaptuzumab-PY-VC-MMAD). DR5 is a member of the TNF receptor superfamily that is overexpressed in various solid and hematologic malignancies, including pancreatic cancer and acute lymphoblastic leukemia, while maintaining low expression in normal tissues. Zaptuzumab binds to DR5 on the cell surface, facilitating receptor-mediated internalization and, in the context of an ADC, the lysosomal release of cytotoxic payloads. Additionally, the naked antibody exhibits antitumor activity through the induction of apoptosis and immune-mediated mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).