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Updated: Jul 5, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Development of Recombinant Oncolytic rVSV-mIL12-mGMCSF for Cancer Immunotherapy
Anastasia Ryapolova1, Ekaterina Minskaia1, Nizami Gasanov1
1Department of Gene Therapy, Sirius University of Science and Technology, Olympic Avenue, 1, 354340 Sochi, Russia.
Abstract:
Anti-cancer therapy based on oncolytic viruses (OVs) is a targeted approach that takes advantage of OVs' ability to selectively infect and replicate in tumor cells, activate the host immune response, and destroy malignant cells over healthy ones. Vesicular stomatitis virus (VSV) is known for its wide range of advantages: a lack of pre-existing immunity, a genome that is easily amenable to manipulation, and rapid growth to high titers in a broad range of cell lines, to name a few. VSV-induced tumor immunity can be enhanced by the delivery of immunostimulatory cytokines. The targeted cytokine delivery to tumors avoids the significant toxicity associated with systemic delivery while also boosting the immune response. To demonstrate this enhanced effect on both tumor growth and survival, a novel recombinant VSV (rVSV)-mIL12-mGMCSF, co-expressing mouse IL-12 (interleukin-12) and GM-CSF (granulocyte-macrophage colony-stimulating factor), was tested alongside rVSV-dM51-GFP (rVSV-GFP) that was injected intratumorally in a syngeneic in vivo C57BL/6 mouse model infused subcutaneously with B16-F10 melanoma cells. The pilot study tested the effect of two viral injections 4 days apart and demonstrated that treatment with the two rVSVs resulted in partial inhibition of tumor growth (TGII of around 40%) and an increased survival rate in animals from the treatment groups. The effect of the two VSVs on immune cell populations will be investigated in future in vivo studies with an optimized experimental design with multiple higher viral doses, as a lack of this information presents a limitation of this study.
Insights
Oncolytic viruses (OVs) show promise for cancer therapy. A novel recombinant VSV expressing IL-12 and GM-CSF partially inhibited melanoma tumor growth and improved survival in mice.
Area of Science:
- Oncolytic virotherapy
- Immunotherapy
- Cancer research
Background:
- Oncolytic viruses (OVs) selectively target and destroy cancer cells while stimulating anti-tumor immunity.
- Vesicular stomatitis virus (VSV) is a promising platform due to its lack of pre-existing immunity and ease of genetic manipulation.
- Enhancing OV therapy with cytokine delivery can improve efficacy and reduce systemic toxicity.
Purpose of the Study:
- To evaluate a novel recombinant VSV (rVSV)-mIL12-mGMCSF co-expressing mouse IL-12 and GM-CSF for enhanced anti-cancer effects.
- To assess the impact of intratumoral rVSV administration on melanoma tumor growth and animal survival in a syngeneic mouse model.
Main Methods:
- Intratumoral injection of rVSV-mIL12-mGMCSF and rVSV-dM51-GFP in C57BL/6 mice bearing subcutaneous B16-F10 melanoma.
- Two viral injections were administered 4 days apart in a pilot study.
- Tumor growth inhibition and survival rates were monitored.
Main Results:
- Treatment with both rVSVs resulted in partial inhibition of tumor growth, with a Tumor Growth Inhibition Index (TGII) of approximately 40%.
- Animals in the treatment groups exhibited increased survival rates compared to controls.
- The study demonstrated the potential of co-expressing IL-12 and GM-CSF via rVSV for anti-cancer effects.
Conclusions:
- Recombinant VSV engineered to co-express IL-12 and GM-CSF shows potential as an oncolytic immunotherapy for melanoma.
- Intratumoral delivery of these cytokines via rVSV offers a targeted approach to enhance anti-tumor immunity and improve survival.
- Further studies with optimized designs and higher viral doses are warranted to investigate immune cell population dynamics.
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