4.7 Article

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

Journal

JOURNAL OF MEDICAL VIROLOGY
Volume 92, Issue 12, Pages 3617-3627

Publisher

WILEY
DOI: 10.1002/jmv.25691

Keywords

CRISPR; cytokine; herpes simplex virus

Categories

Funding

  1. National Major Scientific and Technological Special Project for Significant New Drugs Development during the Thirteenth Five-year Plan Period [2018ZX09733002]
  2. National Natural Science Foundation of China [81972308]
  3. Wuhan Leading-edge Fundamental Project for Application [2019020701011438]

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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.

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