CD253. also known as TRAIL (TNF-related apoptosis-inducing ligand) or TNFSF10. is a type II transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily. It plays a critical role in immune surveillance by selectively inducing apoptosis in transformed or infected cells while sparing normal cells. CD253 binds to death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2), triggering caspase-dependent apoptotic pathways. However, some cancer cells evade this mechanism by upregulating decoy receptors (DcR1. DcR2) or anti-apoptotic proteins.
CD253-targeted antibodies, particularly agonistic antibodies against DR4/DR5. have been explored as cancer therapeutics to reactivate apoptosis in resistant tumors. Early clinical trials demonstrated limited efficacy due to tumor heterogeneity, resistance mechanisms, and off-target effects. Recent strategies focus on combination therapies with chemotherapy, immune checkpoint inhibitors, or sensitizing agents to enhance potency. Conversely, anti-CD253 antibodies that neutralize TRAIL have been studied in autoimmune and inflammatory diseases, where excessive TRAIL signaling may contribute to tissue damage.
Research continues to optimize antibody design, including bispecific formats or engineered Fc regions to improve receptor clustering and immune cell engagement. Despite challenges, CD253 remains a promising target for precision oncology and immune modulation.