STING agonist diABZI enhances the cytotoxicity of T cell towards cancer cells

Antigen-specific T cell receptor-engineered T cell (TCR-T) immunotherapy has shown significant effectiveness in fighting cancer. Recent research suggests that enhancing communication between the innate and adaptive immune systems may be essential for optimizing long-term antigen-specific immunity, with the stimulator of interferon genes (STING) emerging as a promising target in cancer immunotherapy. The recognition and destruction of tumor cells by TCR-T cells depend on the level of antigen expression or presentation in these cells. This study aimed to explore the potential of innate immune stimulation in T cells and engineered T cells to improve immunotherapy against cancer cells with low antigen expression. We systematically investigated how the STING agonist diABZI interacts with the adaptive immune system. Using NY-ESO-1 full knockout Mel526 cells, we discovered that diABZI activates both the STING-mediated and TCR signaling pathways. Flow cytometry results further showed that STING agonist diABZI enhanced antigen presentation in cancer cells, thereby increasing the effectiveness of TCR-T cells against tumors both in vitro and in vivo. Our findings demonstrate that diABZI boosts the efficacy of TCR-T immunotherapy by activating STING-mediated and TCR signaling pathways, enhancing interferon-γ expression, and improving antigen presentation in tumor cells. This suggests that STING agonists diABZI STING agonist could be a valuable strategy for enhancing TCR-T cancer immunotherapy.