Effects of intravenously administered recombinant vesicular stomatitis virus (VSV(deltaM51)) on multifocal and invasive gliomas.

Full Abstract

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.

Author information

Author/s: Lun, XueQing (X); Senger, Donna L (DL); Alain, Tommy (T); Oprea, Andra (A); Parato, Kelley (K); Stojdl, Dave (D); Lichty, Brian (B); Power, Anthony (A); Johnston, Randal N (RN); Hamilton, Mark (M); Parney, Ian (I); Bell, John C (JC); Forsyth, Peter A (PA);

Affiliation: Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of the National Cancer Institute (J Natl Cancer Inst), published in United States. (Language: eng)

Reference: 2006-Nov; vol 98 (issue 21) : pp 1546-57

Dates: Created 2006/11/01; Completed 2006/11/27;

PMID: 17077357, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Antineoplastic Agents - administration & dosage
Blotting, Western
Brain Neoplasms - drug therapy; pathology; therapy
Cell Line, Tumor
Disease Models, Animal
Fluorescent Dyes
Gene Expression Regulation, Neoplastic
Glial Fibrillary Acidic Protein - metabolism
Glioma - drug therapy; pathology; therapy
Humans
Immunohistochemistry

Associated Chemicals: Antineoplastic Agents (0) ; Fluorescent Dyes (0) ; Glial Fibrillary Acidic Protein (0) ; Luminescent Proteins (0) ; M protein, Vesicular stomatitis virus (0) ; Recombinant Proteins (0) ; Viral Matrix Proteins (0) ; red fluorescent protein (0)

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