The construction of a new oncolytic herpes simplex virus expressing murine interleukin‐15 with gene‐editing technology
Linkang Cai, Han Hu, Haixiao Duan, Yuying Li, Zongxing Zou, Kailun Luo, Ziyi Zhang, Junhan Yang, Jing Jin, Ying Chen, Zonghuang Ke, Zongyao Fang, Qiong Liu, Xiaoqian Hong, Sheng Hu, Binlei Liu
Abstract
The treatment of tumors with oncolytic viruses is an important cancer immunotherapy strategy. Interleukin-15 (IL-15) can enhance the antitumor effect of natural killer cells and T cells. An oncolytic herpes simplex type II virus (oHSV2-mIL-15CherryFP) expressing mouse IL-15 was constructed using the CRISPR/Cas9 system, and its antitumor activity in vitro and in vivo was evaluated. In vitro, the mouse interleukin-15 (mIL-15) present in the culture supernatant expressed by oHSV2-mIL-15CherryFP was able to enhance the killing of CT26-GFP tumor cells by T cells. In addition, the intratumoral injection of oHSV2-mIL-15CherryFP inhibited tumor growth in the CT26-iRFP and BGC823-iRFP model. These results indicate that the use of oncolytic herpes simplex virus expressing IL-15 may be a potential therapeutic strategy in tumor immunotherapy.