Mechanisms of VSV-mediated Oncolysis

Project: Research project

Description

DESCRIPTION (provided by applicant): 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.
StatusFinished
Effective start/end date4/1/027/31/12

Funding

  • National Institutes of Health: $287,658.00
  • National Institutes of Health: $303,379.00
  • National Institutes of Health: $299,221.00
  • National Institutes of Health: $299,221.00
  • National Institutes of Health: $303,379.00
  • National Institutes of Health: $296,249.00
  • National Institutes of Health: $303,379.00

Fingerprint

Receptor-Interacting Protein Serine-Threonine Kinases
Death Domain Receptors
Vesicular Stomatitis
Neoplasms
Protein Kinases
Interferons
Viruses
Genes
Interferon-beta
RNA Viruses
Constitution and Bylaws
Interferon Regulatory Factor-3
Toll-Like Receptor 3
Therapeutics
RNA Helicases
Melanoma-Specific Antigens
Interferon Type I
Cell Death
Differentiation Antigens
Tretinoin

ASJC

  • Medicine(all)