Journal
CANCER RESEARCH
Volume 74, Issue 13, Pages 3567-3578Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-13-3306
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Funding
- Wilhelm-Sander-Foundation
- Deutsche Forschungsgemeinschaft
- Hertie Foundation
- FWF Austrian Science Fund [P25499-B-13]
- LOEWE Center for Cell and Gene Therapy Frankfurt
- Schering Foundation
- Austrian Science Fund (FWF) [P 25499] Funding Source: researchfish
- Austrian Science Fund (FWF) [P25499] Funding Source: Austrian Science Fund (FWF)
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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. (C) 2014 AACR.
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