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

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

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.

Keywords: CRISPR; cytokine; herpes simplex virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Cas Systems
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Gene Editing* / methods
  • Herpesvirus 2, Human / genetics
  • Herpesvirus 2, Human / immunology
  • Humans
  • Immunotherapy / methods
  • Interleukin-15* / genetics
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Oncolytic Virotherapy* / methods
  • Oncolytic Viruses* / genetics
  • T-Lymphocytes / immunology

Substances

  • Interleukin-15