Grant: Doctoral Research Award: Canada Graduate Scholarships

Immunotherapies often fail in cancers that no longer present a molecule called MHC-I on their cell surface. Such loss of MHC-I allows cancers escape from the killer lymphocytes that are key mediators of the immune system's fight against cancers. Restoring MHC-I could render these cancers susceptible to immunotherapy, but this remains an unachieved goal. Research has identified that diverse types of cancers shut down their expression of NLRC5, which is the key inducer of MHC-I expression. Indeed, NLRC5 deficient cancers show fewer immune cells, high malignancy and resistance to immunotherapy. Our laboratory has developed a version of NLRC5 called NLRC5-Superactivator (NLRC5-SA), which displays superior ability to induce MHC-I in cancer cells and control tumor growth in mouse models. The goal of my project is to find ways to deliver NLRC5-SA to tumors. For this purpose, I will use oncolytic viruses that specifically target tumor cells, leaving normal cells untouched. We have developed an oncolytic virus bearing NLRC5-SA (VV-NLRC5-SA) and validated its ability to induce MHC-I. In the next three years, I will test the ability of VV-NLRC5-SA injected into different types of tumors to induce MHC-I expression, attract lymphocytes cause tumor shrinkage and establish antitumor immunity. This project will lay the foundations to produce a self-perpetuating cancer immunotherapeutic that would be ready-to-serve, cost-effective and universally applicable to a variety of cancers that evade immune destruction via reducing their MHC-I expression.