采用基因编辑技术构建表达鼠白细胞介素-15 的新型溶瘤单纯疱疹病毒。

The construction of a new oncolytic herpes simplex virus expressing murine interleukin-15 with gene-editing technology.

机构信息

National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, China.

Wuhan Binhui Biotechnology Co. Ltd., Wuhan, China.

出版信息

J Med Virol. 2020 Dec;92(12):3617-3627. doi: 10.1002/jmv.25691. Epub 2020 Feb 14.

DOI:10.1002/jmv.25691

PMID:31994741

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.

摘要

溶瘤病毒治疗肿瘤是一种重要的癌症免疫治疗策略。白细胞介素-15（IL-15）可以增强自然杀伤细胞和 T 细胞的抗肿瘤作用。使用 CRISPR/Cas9 系统构建了表达小鼠白细胞介素-15（mIL-15）的单纯疱疹病毒 II 型（oHSV2-mIL-15CherryFP），并评估了其在体外和体内的抗肿瘤活性。在体外，oHSV2-mIL-15CherryFP 表达的培养上清液中的小鼠白细胞介素-15（mIL-15）能够增强 T 细胞对 CT26-GFP 肿瘤细胞的杀伤作用。此外，oHSV2-mIL-15CherryFP 的瘤内注射抑制了 CT26-iRFP 和 BGC823-iRFP 模型中的肿瘤生长。这些结果表明，使用表达白细胞介素-15 的溶瘤单纯疱疹病毒可能是肿瘤免疫治疗的一种潜在治疗策略。