Grant: Project Grant

Cancers deploy diverse mechanisms to escape killing by the immune system. An important mechanism of such immune evasion is the loss of expression of a protein called MHC class-I, which is crucial to activate antitumor killer lymphocytes. MHC-I expression is critically dependent on another protein called NLRC5. Thus, many cancers suppress NLRC5 expression as a key immune evasion mechanism. We have shown that restoring NLRC5 expression in tumors elicits antitumor immunity and causes tumor clearance. This raises the possibility of exploiting NLRC5 for cancer immunotherapy. To achieve this goal, we will use an engineered version of NLRC5 called NLRC5-SA that is very efficient in inducing antitumor immunity and clearing the tumor masses in experimental animals. We have also developed delivery vehicles to express NLRC5-SA within tumors in order to elicit antitumor immunity. In the proposed project, we will gain a deeper understanding of the mechanisms by which NLRC5-SA expression in tumors promotes efficient antitumor immunity. We will also test the efficiency of NLRC5-SA delivery vehicles in causing tumor regression, and in establishing antitumor immunity using mouse tumor models and human prostate cancer models.