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

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.

Highlights

Newcastle disease virus (NDV) belongs to the genus Avulavirus.[1]
Gene sequencing showed that insertion of IL-24 did not induce any mutation during virus construction
The results showed that B16-LX/IL-24 could not provide any increased preventive effects against EL-4 cells, as compared with irradiated B16-immunized mice (Figure 4C), suggesting that the antitumor response induced by LX/IL-24-modified tumor cells was specific to autologous tumor

Summary

Introduction

NDV can be divided into two types (lytic and nonlytic) according to the pattern of infection in tumor cells. Lytic NDV produced infectious particles that could infect other tumor cells, while nonlytic NDV produced uninfectious particles.[10,11,12] Lytic NDV is often used to lyse tumor cells directly, while nonlytic NDV is often used to modify tumor cells to use as vaccine (autologous tumor vaccines [ATVs] modified with NDV [ATV-NDVs]).[13,14] The therapeutic effects of ATV-

Methods

Results

Conclusion