Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy

Oncolytic viral therapy is an emerging new class of immunotherapy that involves selectively infecting and killing tumor cells. Several oncolytic viruses (OVs) have exhibited promising potential for treating human cancer in animal models and clinical trials, including hepatocellular carcinoma (HCC). However, despite clinical evidence and benefit for patients, the cost-intensive manufacturing and testing nature of oncolytic viral products makes them far out of reach for most US patients. We propose to develop a cost-effective immunovirotherapy approach that could synergize with other therapies to improve the outcomes for patients with advanced HCC. Specifically, we showed that intratumoral administration of low doses of the live attenuated measles, mumps and rueball viruses (MMR) vaccine effectively activates a robust cytotoxic T cells response, leading to tumor regression and extended survival in the syngeneic HCC model. Using transcriptomic approach, we showed that mechanistically MMR exerts its anti-tumor activity by priming innate and adaptive anti-tumor immune responses, leading to immunologically coordinated death of cancer cells. The proposed research can impact cancer patients globally, and our multidisciplinary team is uniquely equipped to execute the proposed studies. Overall design: Anti-tumor mechanism of MMR in hepatocellular cancer