Science subjournal: intratumoral injection of oncolytic viruses encoding IL-7 and IL-12 can increase the antitumor efficacy of immunocheckpoint inhibitors

January 18, 2020 / Biovalley BIOON / - -- oncolytic virus such as oncolytic vaccinia virus is a virus that can kill cancer cells In recent years, oncolytic viruses have attracted more and more attention with the development of biological and immune methods in the field of cancer The immune state in tumor microenvironment is the key index to determine the antitumor efficacy of immunotherapy Existing data support the role of tumor infiltrating lymphocyte (TIL) activation and proliferation in improving the therapeutic benefits of immunotherapy for solid tumor patients In a new study, in order to further improve the anti-cancer potential of oncolytic virus, researchers from Japan's University of ornithology and astralas Pharma Inc genetically modified oncolytic vaccinia virus to deliver two cytokines, IL-7 and IL-12, to help stimulate the anti-tumor immune response The relevant research results were published in the Journal of Science Translational Medicine on January 15, 2020 The title of the paper is "internal expression of IL-7 and IL-12 using an online virus includes systematic sensitivity to immune checkpoint blockade" The corresponding author of the paper is Shinsuke Nakao of anstelai pharmaceutical company Picture from Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aax7992 Nakao and his team found that selective injection of oncolytic vaccinia virus encoding IL-7 and IL-12 into tumor bearing mice with immune activity can activate the inflammatory immune state of tumors with poor immunogenicity before, and even lead to complete tumor regression, even for tumors accumulating in the distance Mice that achieved complete tumor regression developed resistance when they were attacked by the same tumor cells again, which indicated that they established long-term tumor specific immune memory In the tumor model of unresponsiveness to single drug of immunocheckpoint inhibitor anti-PD-1 or anti-CTLA4 antibody, the combination of this virus therapy with anti-PD-1 or anti-CTLA4 antibody can further improve the anti-tumor activity compared with the only use of this virus therapy These findings indicate that by changing the immune status of tumor microenvironment, the oncolytic vaccinia virus with genes encoding IL-7 and IL-12 has antitumor activity in the tumor directly injected with the oncolytic vaccinia virus and in the distant tumor not injected with the oncolytic vaccinia virus, which makes the tumor sensitive to immunosuppressant Nakao's team also observed the benefits of tumor expression of IL-7 and IL-12 in humanized mice carrying human cancer cells These data support further studies in patients with uninflammatory solid tumors (BIOON Com) reference: shinsukenakao et al Internal expression of IL-7 and IL-12 using an online virus increases systematic sensitivity to immune checkpoint blockade Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aax7992