Tumor growth inhibition by intratumoral inoculation of defective herpes simplex virus vectors expressing granulocyte - Macrophage colony-stimulating factor

Masahiro Toda, Robert L. Martuza, Samuel D. Rabkin

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

To evaluate the potential of defective herpes simplex virus (HSV) amplicon vectors as in vivo cytokine gene transfer vehicles for active immunotherapy, we generated a defective HSV vector that encodes the murine granulocyte - macrophage colony-stimulating factor (GM-CSF) gene, using a replication-defective HSV as helper virus. A variety of murine tumor cell lines were efficiently infected in vitro with the defective GM-CSF vector (dvGM), and this led to the synthesis and secretion of murine GM-CSF. In an established bilateral subcutaneous tumor model with Harding-Passey murine melanoma, unilateral intratumoral inoculation of dvGM significantly inhibited tumor growth of both the inoculated and noninoculated contralateral tumors. This tumor inhibition was dose-dependent and resulted in increased survival of the dvGM-treated mice. Inoculation of a lacZ-expressing defective vector had no effect on tumor growth. We conclude that this defective HSV vector system offers an effective method for cytokine gene delivery in vivo and that GM-CSF expression in tumors has antitumor activity.

Original languageEnglish
Pages (from-to)324-329
Number of pages6
JournalMolecular Therapy
Volume2
Issue number4
DOIs
Publication statusPublished - 2000 Oct
Externally publishedYes

Keywords

  • Cancer therapy
  • GM-CSF
  • Harding-Passey
  • Herpes simplex virus
  • Melanoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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