Gene therapy for brain tumors: Regression of experimental gliomas by adenovirus-mediated gene transfer in vivo

Shu Hsia Chen, H. David Shine, J. Clay Goodman, Robert G. Grossman, Savio L C Woo

Research output: Contribution to journalArticle

467 Scopus citations

Abstract

The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6 glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6 glioma cells were efficiently transduced in vitro by a replicative-defective recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic intracerebral injection of 1 x 104 C6 cells in nude mice. After 8 days of tumor growth, 3 x 108 ADV/RSV-tk viral particles were injected into the tumors and the mice subsequently were treated with GCV for 6 days. Tumor size in untreated and treated animals was compared 20 days after tumor implantation. The mean cross-sectional area of the tumors in the treated animals was 23-fold smaller than in control animals and the tumor volume was reduced by >500-fold. These results demonstrate that the recombinant adenoviral vector can function as an efficient gene delivery vehicle for the treatment of gliomas by in vivo gene therapy.

Original languageEnglish (US)
Pages (from-to)3054-3057
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number8
DOIs
StatePublished - Apr 12 1994

Keywords

  • ganciclovir
  • herpes simplex virus thymidine kinase

ASJC Scopus subject areas

  • Genetics
  • General

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