TNFSF10. also known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), is a member of the TNF superfamily that plays a critical role in regulating apoptosis through interaction with death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2). These receptors trigger extrinsic apoptotic pathways upon ligand binding, making TNFSF10 a key mediator of immune surveillance against tumor cells and infected cells. However, many cancers develop resistance to TRAIL-induced apoptosis by upregulating decoy receptors (DcR1/DcR2) or anti-apoptotic proteins.
TNFSF10 antibodies are tools designed to either mimic or modulate TRAIL activity. Agonistic antibodies targeting DR4/DR5 (e.g., mapatumumab, lexatumumab) aim to induce apoptosis in cancer cells by clustering death receptors, showing potential in preclinical and clinical oncology studies. Conversely, inhibitory antibodies blocking TNFSF10 or its receptors may help manage autoimmune or inflammatory conditions where excessive apoptosis occurs. These antibodies are widely used in research to study TRAIL signaling dynamics, cancer resistance mechanisms, and therapeutic targeting strategies.
Despite promising early results, clinical translation faces challenges like tumor selectivity, systemic toxicity, and variable patient responses. Current research focuses on antibody engineering (e.g., Fc modifications), combination therapies with chemotherapeutic agents, and biomarkers for patient stratification. Commercially available TNFSF10 antibodies also serve as essential reagents for immunohistochemistry, flow cytometry, and Western blotting in basic research.