Tumor Cells Modified with Newcastle Disease Virus Expressing IL-24 as a Cancer Vaccine

Xiaojing Xu; Cheng Yi; Xiaoqin Yang; Jianwei Xu; Qing Sun; Yonghao Liu; Lixiang Zhao

doi:10.1016/j.omto.2019.06.001

Tumor Cells Modified with Newcastle Disease Virus Expressing IL-24 as a Cancer Vaccine

Mol Ther Oncolytics. 2019 Jun 12:14:213-221. doi: 10.1016/j.omto.2019.06.001. eCollection 2019 Sep 27.

Authors

Xiaojing Xu¹, Cheng Yi¹, Xiaoqin Yang¹, Jianwei Xu^{2

3}, Qing Sun^{4

5}, Yonghao Liu⁶, Lixiang Zhao¹

Affiliations

¹ College of Basic Medicine and Biological Sciences, Medical Department, Soochow University, 215123 Suzhou, China.
² National Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Center for Tissue Engineering and Stem Cell Research, Guizhou Province Key Laboratory of Regenerative Medicine, Guizhou Medical University, 550004 Guiyang, Guizhou, China.
³ Laboratory of Adult Stem Cell Translational Research, Chinese Academy of Medical Sciences, Guiyang, Guizhou, China.
⁴ Laboratory of Animal Infectious Diseases, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
⁵ Virus Research Unit, Department of Microbiology and Immunology, School of Medicine, University of Otago, Dunedin, New Zealand.
⁶ Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, 215123 Suzhou, People's Republic of China.

Abstract

Interleukin-24 (IL-24) is a promising agent for cancer immunotherapy that induces apoptosis of tumor cells and enhances T cell activation and function. In order to improve the antitumor activity induced by Newcastle disease virus (NDV)-modified tumor vaccine, we generated a recombinant NDV expressing IL-24 using reverse genetics. Irradiated tumor cells infected with LX/IL-24 showed stable IL-24 expression. The cytotoxicity assay showed that LX/IL-24-infected murine melanoma cells significantly enhanced the antitumor immune response in vitro. Then, the antitumor effects of virus-infected tumor cells were examined in the murine tumor models. LX/IL-24-infected tumor cells exhibited strong antitumor effects both in prophylaxis and therapeutic models. LX/IL-24-infected tumor cells increased infiltration of CD4⁺ T cells and CD8⁺ T cells in tumor sites, and the antitumor activity of the tumor vaccine modified with LX/IL-24 was dependent on CD8⁺ T cells. Taken together, our data well illustrates that LX/IL-24-modified tumor cells are a promising agent for cancer immunotherapy.

Keywords: Newcastle disease virus; T cell; interleukin-24; tumor; vaccine.