A stem-loop RNA RIG-I agonist induces immunogenic death and vascular remodeling to potentiate cancer immunotherapy

The immunoreceptor retinoic acid-induced gene-I (RIG-I) is a promising target molecule for stimulating antitumor innate immunity. In this study, we evaluated the possible mechanisms of RIG-I signaling to make tumors immunogenic in the Renca cancer model. RIG-I is expressed in nucleated cells, including tumor cells, and its activation induces potent CD8 and natural killer (NK) cell responses. We used bulk RNA sequencing to uncovermolecular targets and mechanisms of action behind anti-tumor activity. Mice were randomized into treatment and PBS (vehicle) groups when tumors reached 100 to 150 mm3. Intratumoral injection of nanoparticles containing 3pRNA RIG-I agonist or PBS was performed at 48-hour intervals for a total of 3 treatments. Tumors (5 mice in each group) were harvested after 24 hours of last treatment.