Live-attenuated Japanese encephalitis virus inhibits glioblastoma growth and elicits potent antitumor immunity

Zhongbing Qi; Jing Zhao; Yuhua Li; Bin Zhang; Shichuan Hu; Yanwei Chen; Jinhu Ma; Yongheng Shu; Yunmeng Wang; Ping Cheng

doi:10.3389/fimmu.2023.982180

Live-attenuated Japanese encephalitis virus inhibits glioblastoma growth and elicits potent antitumor immunity

Front Immunol. 2023 Apr 11:14:982180. doi: 10.3389/fimmu.2023.982180. eCollection 2023.

Authors

Zhongbing Qi¹, Jing Zhao², Yuhua Li³, Bin Zhang¹, Shichuan Hu¹, Yanwei Chen¹, Jinhu Ma¹, Yongheng Shu¹, Yunmeng Wang¹, Ping Cheng¹

Affiliations

¹ State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
² Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
³ Department of Arboviruses Vaccine, National Institute for Food and Drug Control, Beijing, China.

Abstract

Glioblastomas (GBMs) are highly aggressive brain tumors that have developed resistance to currently available conventional therapies, including surgery, radiation, and systemic chemotherapy. In this study, we investigated the safety of a live attenuated Japanese encephalitis vaccine strain (JEV-LAV) virus as an oncolytic virus for intracerebral injection in mice. We infected different GBM cell lines with JEV-LAV to investigate whether it had growth inhibitory effects on GBM cell lines in vitro. We used two models for evaluating the effect of JEV-LAV on GBM growth in mice. We investigated the antitumor immune mechanism of JEV-LAV through flow cytometry and immunohistochemistry. We explored the possibility of combining JEV-LAV with PD-L1 blocking therapy. This work suggested that JEV-LAV had oncolytic activity against GBM tumor cells in vitro and inhibited their growth in vivo. Mechanistically, JEV-LAV increased CD8+ T cell infiltration into tumor tissues and remodeled the immunosuppressive GBM microenvironment that is non-conducive to immunotherapy. Consequently, the results of combining JEV-LAV with immune checkpoint inhibitors indicated that JEV-LAV therapy improved the response of aPD-L1 blockade therapy against GBM. The safety of intracerebrally injected JEV-LAV in animals further supported the clinical use of JEV-LAV for GBM treatment.

Keywords: aPD-L1; anti-tumor immunity; glioblastoma; live-attenuated Japanese encephalitis vaccine virus; oncolytic virotherapy; oncolytic virus.

Publication types

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

MeSH terms

Animals
Encephalitis Virus, Japanese*
Glioblastoma* / therapy
Immunotherapy
Japanese Encephalitis Vaccines*
Mice
Oncolytic Viruses*
Tumor Microenvironment

Substances

Japanese Encephalitis Vaccines

Grants and funding

This work was supported by the National Science and Technology Major Projects of New Drugs (2018ZX09201018-013), the National Science and Technology Major Project for Infectious Diseases Control (2017ZX10203206-004), the National Natural Science Foundation of China (81101728).