Recent data from our laboratory has shown that vesicular stomatitis virus, VSV, a relatively non-pathogenic, negative-stranded RNA virus, can selectively induce the cytolysis of malignant cells, but not normal cells, through the induction of apoptotic cell death. VSV appears able to selectively replicate in transformed cells since these hosts exhibit the hallmarks of a flawed interferon (IFN) system, which is essential for preventing VSV replication. The simple genetic constitution of VSV, lack of any known transforming properties, extensive immunobiology data and the ability to genetically manipulate the organism affords an ideal opportunity to further enhance the oncolytic potential of this innocuous virus. Thus, aside from preferentially targeting malignant cells and possessing direct antitumor activity, VSV recombinants could be generated that could increase a tumors susceptibility to chemotherapeutic agents and/or the host immune response. Collectively, our data demonstrates that VSV could provide a promising and exciting approach to cancer therapy.
Aim I is to confirm possible defects in the interferon and other pathway(s) such as the regulation of translation in malignant cells, which may be mechanistically responsible for allowing VSV to exert its oncolytic activity.
Aim II will further evaluate the efficacy and safety, in tumor therapy, of recombinant VSVs that express genes that may facilitate greater oncolytic ability, such as the IFN-beta gene. Our novel data should provide information on the ability of rVSVs to function as a safe therapy for the potential treatment of Cancer. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA095924-05
Application #
7226700
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Program Officer
Muszynski, Karen
Project Start
2003-07-01
Project End
2008-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
5
Fiscal Year
2007
Total Cost
$287,658
Indirect Cost
Name
University of Miami School of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
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