IL-36γ-armed oncolytic virus exerts superior efficacy through induction of potent adaptive antitumor immunity

Author:

Yang Min,Giehl Esther,Feng Chao,Feist Mathilde,Chen Hongqi,Dai Enyong,Liu Zuqiang,Ma Congrong,Ravindranathan Roshni,Bartlett David L.,Lu Binfeng,Guo Zong ShengORCID

Abstract

AbstractIn this study, we aimed to apply the cytokine IL-36γ to cancer immunotherapy by constructing new oncolytic vaccinia viruses (OV) expressing interleukin-36γ (IL-36γ-OVs), leveraging unique synergism between OV and IL-36γ’s ability to promote antitumor adaptive immunity and modulate tumor microenvironment (TME). IL-36γ-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-36γ-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 IL36γ-armed OVs exert potent therapeutic efficacy mainly though antitumor immunity and they may hold great potential to advance treatment in human cancer patients.

Funder

National Institutes of Health

UPMC Immune Transplant and Therapy Center

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Oncology,Immunology,Immunology and Allergy

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