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Effects of intravenously administered recombinant vesicular stomatitis virus (VSV(deltaM51)) on multifocal and
XueQing Lun1, Donna L Senger, Tommy Alain
1Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
Background:
An ideal virus for the treatment of cancer should have effective delivery into multiple sites within the tumor, evade immune responses, produce rapid viral replication, spread within the tumor, and infect multiple tumors. Vesicular stomatitis virus (VSV) has been shown to be an effective oncolytic virus in a variety of tumor models, and mutations in the matrix (M) protein enhance VSV's effectiveness in animal models.
Methods:
We evaluated the susceptibility of 14 glioma cell lines to infection and killing by mutant strain VSV(deltaM51), which contains a single-amino acid deletion in the M protein. We also examined the activity and safety of this strain against the U87 and U118 experimental models of human malignant glioma in nude mice and analyzed the distribution of the virus in the brains of U87 tumor-bearing mice using fluorescence labeling. Finally, we examined the effect of VSV(deltaM51) on 15 primary human gliomas cultured from surgical specimens. All statistical tests were two-sided.
Results:
All 14 glioma cell lines were susceptible to VSV(deltaM51) infection and killing. Intratumoral administration of VSV(deltaM51) produced marked regression of malignant gliomas in nude mice. When administered systemically, live VSV(deltaM51) virus, as compared with dead virus, statistically significantly prolonged survival of mice with unilateral U87 tumors (median survival: 113 versus 46 days, P = .0001) and bilateral U87 tumors (median survival: 73 versus 46 days, P = .0025). VSV(deltaM51) infected multifocal gliomas, invasive glioma cells that migrated beyond the main glioma, and all 15 primary human gliomas. There was no evidence of toxicity.
Conclusions:
Systemically delivered VSV(deltaM51) was an effective and safe oncolytic agent against laboratory models of multifocal and invasive malignant gliomas, the most challenging clinical manifestations of this disease.
Insights
A modified vesicular stomatitis virus (VSV) effectively targets and destroys malignant gliomas. This oncolytic virus shows promise for treating challenging brain tumors, demonstrating safety and efficacy in preclinical models.
Area of Science:
- Oncolytic virology
- Cancer therapy
- Neuro-oncology
Background:
- Ideal oncolytic viruses require efficient tumor delivery, immune evasion, and tumor spread.
- Vesicular stomatitis virus (VSV) is a promising oncolytic virus, with matrix (M) protein mutations enhancing its efficacy.
Purpose of the Study:
- To evaluate the efficacy and safety of a mutant VSV strain, VSV(deltaM51), against malignant gliomas.
- To assess VSV(deltaM51)'s activity in preclinical models of human glioma.
Main Methods:
- Assessed susceptibility of 14 glioma cell lines to VSV(deltaM51).
- Evaluated intratumoral and systemic administration of VSV(deltaM51) in nude mice with U87/U118 human malignant glioma xenografts.
- Analyzed viral distribution in tumors and tested VSV(deltaM51) on primary human gliomas.
Main Results:
- All tested glioma cell lines were susceptible to VSV(deltaM51) infection and killing.
- Systemic administration of live VSV(deltaM51) significantly prolonged survival in mice with malignant glioma xenografts.
- VSV(deltaM51) effectively infected multifocal, invasive glioma cells, and all tested primary human gliomas without observed toxicity.
Conclusions:
- Systemically delivered VSV(deltaM51) is a safe and effective oncolytic agent for multifocal and invasive malignant gliomas.
- VSV(deltaM51) demonstrates potential for treating challenging clinical manifestations of glioma.
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