Oncolytic activity of vesicular stomatitis virus is effective against tumors exhibiting aberrant p53, Ras, or Myc function and involves the inductionof apoptosis

We have recently shown that vesicular stomatitis virus (VSV) exhibits poten t oncolytic activity both in vitro and in vivo (S. Balachandran and G. N. B arber, 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 acti vity involved the induction of multiple caspase-dependent apoptotic pathway s was effective in the absence of any significant cytotoxic T-lymphocyte re sponse, and occurred despite normal PKR activity and eIF2 alpha phosphoryla tion. In addition, VSV caused significant inhibition of tumor growth when a dministered intravenously in immunocompetent hosts. Our data indicate that VSV shows significant promise as an effective oncolytic agent against a wid e variety of malignant diseases that harbor a diversity of genetic defects.