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Updated: Dec 29, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
The construction of a new oncolytic herpes simplex virus expressing murine interleukin-15 with gene-editing
Linkang Cai1, Han Hu1, Haixiao Duan1
1National "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.
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.
Insights
Oncolytic herpes simplex virus engineered to express interleukin-15 (IL-15) enhanced T cell-mediated tumor cell killing in vitro. This engineered virus demonstrated significant tumor growth inhibition in vivo, suggesting a promising cancer immunotherapy approach.
Area of Science:
- Oncology
- Immunotherapy
- Virology
Background:
- Oncolytic viruses are a key cancer immunotherapy strategy.
- Interleukin-15 (IL-15) boosts natural killer and T cell antitumor activity.
Purpose of the Study:
- To construct and evaluate an oncolytic herpes simplex type II virus (oHSV2-mIL-15CherryFP) expressing mouse IL-15 (mIL-15).
- To assess the antitumor efficacy of oHSV2-mIL-15CherryFP in vitro and in vivo.
Main Methods:
- CRISPR/Cas9 gene editing was used to engineer the oHSV2-mIL-15CherryFP.
- In vitro assays measured T cell killing of tumor cells.
- In vivo studies involved intratumoral injection in CT26-iRFP and BGC823-iRFP tumor models.
Main Results:
- The engineered virus secreted mIL-15, enhancing T cell-mediated killing of CT26-GFP tumor cells.
- Intratumoral administration of oHSV2-mIL-15CherryFP significantly inhibited tumor growth in both tested models.
- The virus demonstrated effective antitumor activity in vivo.
Conclusions:
- Oncolytic herpes simplex virus expressing IL-15 is a potential therapeutic strategy for cancer immunotherapy.
- Engineered oncolytic viruses offer a promising avenue for enhancing antitumor immune responses.
