Grant: CIHR Fellowship

Cancer immunotherapy, which induces an effective immune response against tumor cells, has the potential to cure patients of disease. However, ovarian tumors can supress the action of the immune system, and current types of immunotherapy are largely ineffective against this cancer. The aim of the proposed project is to overcome cancer-mediated immunosuppression by delivering a nucleic acid molecule called a microRNA (miR) to ovarian tumors. miRs can regulate the expression of large panels of genes, including those related to immune function. In preliminary experiments, we identified a specific miR (miR-146a) as an activator of the immune system in ovarian cancer. Delivery of miR-146a to ovarian tumors increased the immune response against the tumor cells. We hypothesize that miR-146a will potentiate the effectiveness of two currently used immunotherapy drugs. We will also investigate the mechanisms behind miR-146a-mediated immune stimulation, and whether immunotherapy can be further improved by combined inhibition of immunosuppressive enzymes that are commonly expressed by ovarian tumors. This project was designed with direct clinical translation in mind. The use of miRs as a therapeutic platform has proven effective in other contexts and is currently undergoing clinical trials. In addition, the immunotherapy drugs we will be testing are approved for treatment of other cancers. Delivery of miR-146a to ovarian tumors in an effort to improve the immune response has not previously been attempted, and holds the potential to improve the efficacy of immunotherapy against this deadly disease.