DR4 and DR5 are able to transduce apoptosis signals, which induce formation of the death inducing signaling complex (DISC) and activation of the caspase-8 and mitochondrial pathway. As a type I transmembrane protein, DR5 contains a cytoplasmic death domain and mediates apoptosis upon ligation to TRAIL. Recent studies demonstrated that DR5 might contribute more than DR4 to TRAIL-induced apoptosis in cancer cells that express both death receptors. So DR5 is a key receptor of TRAIL and plays an important role in TRAIL-induced apoptosis. TRAIL has been tested on a number of different tumor cell lines, and the results show that TRAIL induces apoptosis in various tumor cell lines, with no cytotoxicity to many normal cell types, which indicates it as a promising reagent for cancer therapy. Since TRAIL may be toxic to human liver cells, TRAIL agonists can be alternative reagents to kill tumor cells. So it is meaningful to obtain anti-DR5 monoclonal antibodies that can activate apoptosis signal upon binding to DR5 and are used as potential anti-tumor drugs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a tumor-selective apoptosis-inducing cytokine with potential as a cancer therapeutic agent. Its ligation with death receptor 5 (DR5; also called TRAIL-R2 or Killer/DR5) rapidly activates the extrinsic apoptotic pathway, leading to apoptotic cell death. Induction of apoptosis by ligation of endogenous DR5 with its ligands (e.g., TRAIL/DR5) has been recognized as a critical mechanism underlying the body's immune surveillance against tumors and metastases
Wang J, Lin Z, Qiao C, et al. Characterization of a Novel Anti-DR5 Monoclonal Antibody WD1 with the Potential to Induce Tumor Cell Apoptosis. Cellular and Molecular Immunology. 2008;5(1):55-60.