Rescue of nonlytic Newcastle Disease Virus (NDV) expressing IL-15 for cancer immunotherapy

Xiaojing Xu; Qing Sun; Xiao Yu; Lixiang Zhao

doi:10.1016/j.virusres.2017.03.003

Rescue of nonlytic Newcastle Disease Virus (NDV) expressing IL-15 for cancer immunotherapy

Virus Res. 2017 Apr 2:233:35-41. doi: 10.1016/j.virusres.2017.03.003. Epub 2017 Mar 7.

Authors

Xiaojing Xu¹, Qing Sun², Xiao Yu¹, Lixiang Zhao³

Affiliations

¹ College of Basic Medicine and Biological Sciences, Medical Department, Soochow University, 215123 Suzhou, People's Republic of China.
² Laboratory of Animal Infectious Diseases, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, People's Republic of China; Virus Research Unit, Department of Microbiology and Immunology, School of Medicine, University of Otago, New Zealand.
³ College of Basic Medicine and Biological Sciences, Medical Department, Soochow University, 215123 Suzhou, People's Republic of China. Electronic address: zhaolixiang@suda.edu.cn.

PMID: 28286036
DOI: 10.1016/j.virusres.2017.03.003

Abstract

In order to test and enhance the antitumor activity against mice melanoma by NDV-modified tumor vaccine, a recombinant NDV expressing IL-15 (LX/(IL-15)) was generated by reverse genetics. Then, the expression level and biological activity of IL-15 were examined. Our results showed that mice tumor cell lines infected with LX/(IL-15) expressed IL-15 at a high level, and that expressed IL-15 was biologically active. Expression kinetics demonstrated that the highest expression level of IL-15 was at 48h post infection. The cytotoxicity assay showed that murine melanoma cells modified with LX/(IL-15) could significantly enhance the antitumor immune response in vitro. In vivo study also showed that murine melanoma cells modified with LX/(IL-15) could prevent melanoma growth in mice. Taken together, our data strongly indicated that recombinant LX/(IL-15) is a promising agent for cancer immunotherapy both for human and animal.

Keywords: IL-15; Newcastle disease virus; Reverse genetics; Tumor; Vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cancer Vaccines / biosynthesis*
Cancer Vaccines / genetics
Cancer Vaccines / immunology
Coculture Techniques
Cytotoxicity, Immunologic / genetics
Female
Gene Expression
Humans
Immunotherapy / methods
Interleukin-15 / genetics
Interleukin-15 / immunology*
Melanoma, Experimental / genetics
Melanoma, Experimental / immunology
Melanoma, Experimental / pathology
Melanoma, Experimental / therapy*
Mice
Mice, Inbred C57BL
Newcastle disease virus / genetics
Newcastle disease virus / immunology*
Oncolytic Virotherapy / methods
Oncolytic Viruses / genetics
Oncolytic Viruses / immunology*
Reverse Genetics / methods
Skin Neoplasms / genetics
Skin Neoplasms / immunology
Skin Neoplasms / pathology
Skin Neoplasms / therapy*
T-Lymphocytes, Cytotoxic / cytology
T-Lymphocytes, Cytotoxic / immunology
Transgenes

Substances

Cancer Vaccines
Interleukin-15