Journal Article

Effects of Intravenously Administered Recombinant Vesicular Stomatitis Virus (VSV<sup>ΔM51</sup>) on Multifocal and Invasive Gliomas

XueQing Lun, Donna L. Senger, Tommy Alain, Andra Oprea, Kelley Parato, Dave Stojdl, Brian Lichty, Anthony Power, Randal N. Johnston, Mark Hamilton, Ian Parney, John C. Bell and Peter A. Forsyth

in JNCI: Journal of the National Cancer Institute

Volume 98, issue 21, pages 1546-1557
Published in print November 2006 | ISSN: 0027-8874
Published online November 2006 | e-ISSN: 1460-2105 | DOI: http://dx.doi.org/10.1093/jnci/djj413

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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 VSVΔM51, 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 VSVΔM51 on 15 primary human gliomas cultured from surgical specimens. All statistical tests were two-sided. Results: All 14 glioma cell lines were susceptible to VSVΔM51 infection and killing. Intratumoral administration of VSVΔM51 produced marked regression of malignant gliomas in nude mice. When administered systemically, live VSVΔM51 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). VSVΔM51 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 VSVΔM51 was an effective and safe oncolytic agent against laboratory models of multifocal and invasive malignant gliomas, the most challenging clinical manifestations of this disease.

Journal Article.  9457 words.  Illustrated.

Subjects: Medical Oncology

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