Related Experiment Video
Updated: Dec 2, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Antitumor effects of IL-12 and GM-CSF co-expressed in an engineered oncolytic HSV-1
Kyoung-Ju Kim1,2, Dahye Moon1,2, So Jung Kong3,4
1Laboratory of Gene Therapy, Department of Microbiology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Abstract:
Oncolytic viruses selectively replicate and destroy cancer cells while sparing normal cells, prompting their recognition as promising antitumor agents. Herpes simplex virus (HSV) is suitable as an anticancer agent, given its considerable therapeutic gene capacity and excellent safety profile in clinical trials. Interleukin (IL)-12 induces a Th1-type immune response that mediates interferon (IFN)-γ release from natural killer (NK), CD4+ and CD8+ T cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the generation of antigen-presenting cells and promotes dendritic cell differentiation. We established a novel oncolytic HSV-1 (∆6/GM/IL12) co-expressing IL-12 and GM-CSF and tested its effects against a B16-F10 murine melanoma model. ∆6/GM/IL12 administration diminished tumor growth and prolonged survival compared to treatment with ∆6/GM or ∆6/IL12 expressing each individual cytokine. Flow cytometry and histological analysis showed increased activation of CD4+ and CD8+ T cells in ∆6/GM/IL12-treated mice. Enzyme-linked immunosorbent spot assay showed an increase in the phenotypically characterized IFN-γ-producing cell population in ∆6/GM/IL12-treated mice. Moreover, ∆6/GM/IL12 induced a B16-F10-specific cytotoxic immune response that enhanced IFN-γ production by CD3+CD8+ T cells. Therefore, IL-12 and GM-CSF from an engineered oncolytic HSV have a synergistic effect, boosting the immune response to increase their antitumor effects.
Insights
Engineered oncolytic Herpes simplex virus (HSV) expressing Interleukin (IL)-12 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) demonstrated synergistic antitumor effects. This novel oncolytic HSV enhanced immune responses and reduced tumor growth in a melanoma model.
Area of Science:
- Oncolytic virology
- Immunotherapy
- Cancer research
Background:
- Oncolytic viruses offer a promising strategy for cancer treatment by selectively targeting and destroying tumor cells.
- Herpes simplex virus (HSV) is a suitable candidate due to its large gene capacity and established safety.
- Interleukin (IL)-12 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) are key immune-modulating cytokines.
Purpose of the Study:
- To develop and evaluate a novel oncolytic Herpes simplex virus-1 (HSV-1) engineered to co-express IL-12 and GM-CSF.
- To assess the synergistic antitumor efficacy of this dual-cytokine expressing HSV-1 (∆6/GM/IL12) in a preclinical melanoma model.
- To investigate the impact of ∆6/GM/IL12 on the tumor microenvironment and host immune response.
Main Methods:
- Construction of an oncolytic HSV-1 vector (∆6/GM/IL12) expressing both IL-12 and GM-CSF.
- Administration of ∆6/GM/IL12, control vectors (∆6/GM, ∆6/IL12), or vehicle to B16-F10 murine melanoma models.
- Tumor growth assessment, survival analysis, flow cytometry, histological examination, and Enzyme-linked immunosorbent spot (ELISPOT) assays.
Main Results:
- ∆6/GM/IL12 significantly inhibited tumor growth and prolonged survival compared to single-cytokine expressing vectors.
- Enhanced activation of CD4+ and CD8+ T cells was observed in mice treated with ∆6/GM/IL12.
- Increased frequency of interferon (IFN)-γ-producing cells and a B16-F10-specific cytotoxic T cell response were detected.
Conclusions:
- Co-expression of IL-12 and GM-CSF in an oncolytic HSV vector results in synergistic antitumor effects.
- The engineered oncolytic HSV enhances anti-tumor immunity, characterized by robust T cell activation and cytokine production.
- This dual-cytokine approach represents a promising strategy for augmenting the efficacy of oncolytic virotherapy against melanoma.
