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

Despite its rising promise, cancer immunotherapy remains out of reach for many patients because of the extensive cost of manufacturing immunotherapy products. In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulates a potent cytotoxic T-cell antitumor immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma and colorectal cancer. Using an integrated transcriptomic and proteomic approach, we demonstrated that mechanistically, MMR exerts its antitumor activity by priming innate and adaptive antitumor immune responses, leading to immunologically coordinated cancer cells death. Our findings highlight a promising potential for LAVs, such as MMR, to be repurposed as cost-effective cancer immunotherapy. ### Competing Interest Statement The authors have declared no competing interest. * ALP : alkaline phosphatase ALT : alanine aminotransferase Anti-Measles : anti-measles fusion and hemagglutinin antibody Anti-Mumps : anti-mumps fusion and hemagglutinin antibody Anti-Rubella : anti-rubella envelope glycoprotein E AST : aspartate aminotransferase ATCC : American Tissue Culture Collection CTLs : cytotoxic T lymphocytes CRC : Colorectal cancer DMEM : Dulbecco modified eagle medium DPBS : dulbecco phosphate-buffered saline ELISA : enzyme-linked immunosorbent assay G-MDSCs : granulocytic myeloid-derived suppressor cells GzmB : granzyme B h : human HCC : hepatocellular carcinoma HGB : hemoglobin LAV : live attenuated viral vaccine MOI : multiplicity of infection PBS : phosphate-buffered saline PD-1 : programmed cell death protein 1 PE : phycoerythrin RNA : ribonucleic acid TAMs : tumor-associated macrophages IT : intratumoral