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Cancer Res. 2014 Jul 1;74(13):3567-78. doi: 10.1158/0008-5472.CAN-13-3306. Epub 2014 May 8.

Re-engineering vesicular stomatitis virus to abrogate neurotoxicity, circumvent humoral immunity, and enhance oncolytic potency.

Author information

1
Authors' Affiliations: Georg-Speyer-Haus, Frankfurt am Main, Germany;
2
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research;
3
Department of Biomedicine, University of Bergen;
4
Institute for Virology, Innsbruck Medical University, Innsbruck, Austria.
5
Apoptosis Research Centre, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
6
Department of Biomedicine, University of Bergen; Department of Pathology, Haukeland University Hospital, Bergen, Norway; and.
7
Institute for Virology, Innsbruck Medical University, Innsbruck, Austria dorothee.von-Laer@i-med.ac.at.

Abstract

As cancer treatment tools, oncolytic viruses (OV) have yet to realize what some see as their ultimate clinical potential. In this study, we have engineered a chimeric vesicular stomatitis virus (VSV) that is devoid of its natural neurotoxicity while retaining potent oncolytic activity. The envelope glycoprotein (G) of VSV was replaced with a variant glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP), creating a replicating therapeutic, rVSV(GP), that is benign in normal brain but can effectively eliminate brain cancer in multiple preclinical tumor models in vivo. Furthermore, it can be safely administered systemically to mice and displays greater potency against a spectrum of human cancer cell lines than current OV candidates. Remarkably, rVSV(GP) escapes humoral immunity, thus, for the first time, allowing repeated systemic OV application without loss of therapeutic efficacy. Taken together, rVSV(GP) offers a considerably improved OV platform that lacks several of the major drawbacks that have limited the clinical potential of this technology to date.

PMID:
24812275
DOI:
10.1158/0008-5472.CAN-13-3306
[Indexed for MEDLINE]
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