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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 8; pp. 3054 - 3057
• Main Authors: Chen, S H, Shine, H D, Goodman, J C, Grossman, R G, Woo, S L
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 12.04.1994; National Acad Sciences; National Academy of Sciences
• 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; Antineoplastic agent; Acyclic nucleoside; Rat; Alphaherpesvirinae; Recombinant DNA; Transfection; Herpesvirus hominis; Tumor cell; Intracranial; Thymidine kinase; Nervous system diseases; Glial cell; Enzyme; Herpesviridae; Transferases; Rodentia; Malignant tumor; Virus; Vertebrata; Cell line; Mammalia; Glioma; Animal; Central nervous system disease; Gene therapy
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.8.3054

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.