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 journalArticlepeer-review

84 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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