IL-36γ-armed oncolytic virus exerts superior efficacy through induction of potent adaptive antitumor immunity
Min Yang, Esther Giehl, Chao Feng, Mathilde Feist, Hongqi Chen, Enyong Dai, Zuqiang Liu, Congrong Ma, Roshni Ravindranathan, David L. Bartlett, Binfeng Lu, Zong Sheng Guo
Abstract
Abstract In this study, we aimed to apply the cytokine IL-36 γ to cancer immunotherapy by constructing new oncolytic vaccinia viruses (OV) expressing interleukin-36 γ (IL-36 γ -OVs), leveraging unique synergism between OV and IL-36 γ ’s ability to promote antitumor adaptive immunity and modulate tumor microenvironment (TME). IL-36 γ -OV had dramatic therapeutic efficacies in multiple murine tumor models, frequently leading to complete cancer eradication in large fractions of mice. Mechanistically, IL-36- γ -armed OV induced infiltration of lymphocytes and dendritic cells, decreased myeloid-derived suppressor cells and M2-like tumor-associated macrophages, and T cell differentiation into effector cells. Further study showed that IL-36 γ -OV increased the number of tumor antigen-specific CD4 + and CD8 + T cells and the therapeutic efficacy depended on both CD8 + and CD4 + T cells. These results demonstrate that these IL36 γ -armed OVs exert potent therapeutic efficacy mainly though antitumor immunity and they may hold great potential to advance treatment in human cancer patients.