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Enhanced oncolytic activity of vesicular stomatitis virus encoding SV5-F protein against prostate cancer

Guimin Chang1, Shuping Xu, Makiko Watanabe

  • 1Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania 15232, USA.

The Journal of Urology
|February 23, 2010
PubMed
Abstract

Insights

Engineered vesicular stomatitis virus (VSV) shows promise as an oncolytic agent. The recombinant virus, rVSV-DeltaG-SV5-F, demonstrated enhanced efficacy against prostate cancer cells in preclinical models.

Area of Science:

  • Oncolytic virotherapy
  • Molecular virology
  • Cancer immunotherapy

Background:

  • Vesicular stomatitis virus (VSV) is explored for cancer therapy due to its tumor-specific replication.
  • Wild-type VSV's immunogenicity and neurotropism limit its clinical use.
  • Replication-restricted VSV vectors offer a safer alternative for oncolytic applications.

Purpose of the Study:

  • To construct and evaluate a replication-restricted VSV encoding SV5-F (rVSV-DeltaG-SV5-F) as an oncolytic agent.
  • To assess the enhanced oncolytic properties of rVSV-DeltaG-SV5-F against prostate cancer.
  • To validate its efficacy in an immunocompetent mouse model.

Main Methods:

  • Construction of rVSV-DeltaG-SV5-F by replacing the VSV G gene with SV5-F.
  • In vitro assessment of cytotoxicity using MTT assays and morphological analysis.
  • In vivo evaluation in immunocompetent mice bearing TRAMP-C2 prostate tumors.

Main Results:

  • rVSV-DeltaG-SV5-F exhibited significantly enhanced in vitro apoptotic and cytotoxic effects compared to rVSV-DeltaG-GFP.
  • Intratumoral administration of rVSV-DeltaG-SV5-F significantly reduced tumor load in mice.
  • The enhanced efficacy was observed regardless of initial tumor size.

Conclusions:

  • Recombinant VSV-DeltaG vectors, particularly rVSV-DeltaG-SV5-F, are effective oncolytic agents.
  • This engineered VSV demonstrates significant potential against mouse prostate cancer.
  • The findings support the use of fusogenic VSV vectors in oncolytic virotherapy.

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