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Updated: Dec 21, 2025

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
An Oncolytic Vaccinia Virus Armed with GM-CSF and IL-24 Double Genes for Cancer Targeted Therapy
Lili Deng1, Xue Yang2, Jun Fan1
1NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, People's Republic of China.
Purpose:
Targeted oncolytic vaccinia virus is an attractive candidate for cancer therapy due to its replication causing lysis of infected tumor cells as well as a delivery vector to overexpress therapeutic transgenes. This study constructed a novel oncolytic vaccinia virus carrying granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-24 (IL-24) double genes to improve efficacy for cancer therapy.
Methods:
Vaccinia virus co-expressing GM-CSF and IL-24 based on Chinese Guang9 strain (VG9-GMCSF-IL24) was constructed with disruption of the viral thymidine kinase (TK) gene. The cytotoxicity of VG9-GMCSF-IL24 in various cell lines was assessed by MTT. The synergistic antitumor effect of VG9-GMCSF-IL24 in vivo was assessed on multiple tumor models.
Results:
In vitro cytotoxicity assay showed that VG9-GMCSF-IL24 exerted a strongly cytotoxic effect on cancer cells, but with no significant cytotoxicity to normal cells. Significant tumor growth inhibition and prolonged survival were observed in different tumor models treated with VG9-GMCSF-IL24. Additionally, systemic and specific antitumoral immunity was investigated in vivo, and enhanced antitumor immunity was observed in VG9-GMCSF-IL24-treated mice.
Conclusion:
Our results indicated that VG9-mediated GM-CSF and IL-24 co-expression performed cooperative and overlapping antitumor effect. As a novel and effective therapeutic strategy for cancer, the combination of oncolysis and immunotherapy with vaccinia virus carrying one or more immunostimulatory genes may have a satisfactory clinical application prospect.
Insights
A novel oncolytic vaccinia virus (VG9-GMCSF-IL24) engineered to express GM-CSF and IL-24 demonstrated significant cancer cell killing and enhanced antitumor immunity. This dual-gene therapy shows promise for effective cancer treatment.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Gene therapy
Background:
- Oncolytic vaccinia virus offers dual action: tumor cell lysis and transgene delivery.
- Enhancing oncolytic virus efficacy through co-expression of therapeutic genes is a key research area.
Purpose of the Study:
- To construct a novel oncolytic vaccinia virus (VG9-GMCSF-IL24) co-expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-24 (IL-24).
- To evaluate the in vitro and in vivo antitumor efficacy and immunogenicity of the engineered virus for improved cancer therapy.
Main Methods:
- Construction of VG9-GMCSF-IL24 based on the Guang9 strain with thymidine kinase (TK) gene disruption.
- In vitro cytotoxicity assessment using MTT assay across various cell lines.
- In vivo evaluation of synergistic antitumor effects and survival in multiple tumor models.
Main Results:
- VG9-GMCSF-IL24 exhibited potent cytotoxicity against cancer cells with minimal impact on normal cells.
- Significant inhibition of tumor growth and prolonged survival were observed in treated animal models.
- Enhanced systemic and specific antitumor immunity was detected in mice treated with VG9-GMCSF-IL24.
Conclusions:
- Co-expression of GM-CSF and IL-24 via VG9 virus yields cooperative and overlapping antitumor effects.
- This combined oncolysis and immunotherapy strategy presents a promising therapeutic approach for cancer treatment with potential clinical applications.
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