Gene Therapy for Brain Tumors: Regression of Experimental Gliomas by Adenovirus-Mediated Gene Transfer in vivo

The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6glioma cells were efficiently transduced in vitro by a rep...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-04, Vol.91 (8), p.3054-3057
Main Authors: Chen, S H, Shine, H D, Goodman, J C, Grossman, R G, Woo, S L
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
adenovirus
Adenoviruses
Animals
Antineoplastic agents
Biological and medical sciences
Biotechnology
Brain
Brain Neoplasms - therapy
Cell lines
Cells
Fundamental and applied biological sciences. Psychology
Ganciclovir - pharmacology
Gene therapy
General aspects
Genes
Genetic Therapy - methods
Genetic Vectors
Genetics
Glioma
Glioma - therapy
Health. Pharmaceutical industry
Herpes viruses
Industrial applications and implications. Economical aspects
Injections
Kidney cells
Medical sciences
Mice
Mice, Nude
Neurons
Pharmacology. Drug treatments
Rodents
Therapy
Thymidine Kinase - genetics
Transduction, Genetic
Tumors
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Summary:The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6glioma 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 104C6cells in nude mice. After 8 days of tumor growth, 3 x 108ADV/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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.8.3054