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Journal of Virology, April 2001, p. 3474-3479, Vol. 75, No. 7
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.7.3474-3479.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Oncolytic Activity of Vesicular Stomatitis Virus Is Effective
against Tumors Exhibiting Aberrant p53, Ras, or Myc Function
and Involves the Induction of Apoptosis
Siddharth
Balachandran,
Mercedes
Porosnicu, and
Glen
N.
Barber*
Department of Microbiology and Immunology and
Sylvester Comprehensive Cancer Center, University of Miami School
of Medicine, Miami, Florida 33136
Received 3 November 2000/Accepted 9 January 2001
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 eIF2
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.
*
Corresponding author. Mailing address: Rm. 514, Papanicolaou Building, 1550 NW 10th Ave. [M710], University of Miami
School of Medicine, Miami, FL 33136. Phone: (305) 243-5914. Fax: (305) 243-5885. E-mail: gbarber{at}med.miami.edu.
Journal of Virology, April 2001, p. 3474-3479, Vol. 75, No. 7
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.7.3474-3479.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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