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AY4 is a novel agonistic monoclonal antibody that targets human death receptor 4 (DR4), also known as tumor necrosis factor receptor superfamily member 10A (TNFRSF10A). Developed by researchers at Ajou University, Yonsei University, and Soonchunhyang University in South Korea, AY4 mimics the activity of the proapoptotic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). It induces apoptosis in cancer cells by triggering the extrinsic apoptotic pathway and generating reactive oxygen species (ROS). Preclinical studies in head and neck cancer models, including KB and HN9 cell lines, have demonstrated that AY4 inhibits cell growth and causes caspase-dependent apoptosis. In vivo administration of AY4 has shown significant tumor growth inhibition in athymic nude mice xenografts, while toxicity testing in zebrafish models indicated no significant embryotoxicity or neurotoxicity at therapeutic doses.
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