Oncolytic activity of vesicular stomatitis virus is effective against tumors exhibiting aberrant p53, Ras, or myc function and involves the induction of apoptosis.
We have recently shown that vesicular stomatitis virus (VSV) exhibits potent oncolytic activity both in vitro and in vivo (S. Balachandran and G. N. Barber, IUBMB Life 50:135-138, 2000). In this study, we further demonstrated, in vivo, the efficacy of VSV antitumor action by showing that tumors that are defective in p53 function or transformed with myc or activated ras are also susceptible to viral cytolysis. The mechanism of viral oncolytic activity involved the induction of multiple caspase-dependent apoptotic pathways was effective in the absence of any significant cytotoxic T-lymphocyte response, and occurred despite normal PKR activity and eIF2alpha phosphorylation. In addition, VSV caused significant inhibition of tumor growth when administered intravenously in immunocompetent hosts. Our data indicate that VSV shows significant promise as an effective oncolytic agent against a wide variety of malignant diseases that harbor a diversity of genetic defects.
Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
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Balachandran
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Porosnicu
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Barber
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D016259:Genes, myc / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology*; D005909:Glioblastoma / Q000821:virology; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000628:therapy*; D010766:Phosphorylation; D051381:Rats; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*; D019892:eIF-2 Kinase / Q000502:physiology
D015852:Eukaryotic Initiation Factor-2; D019892:eIF-2 Kinase