Adenovirus-mediated gene therapy for experimental spinal cord tumors: tumoricidal efficacy and functional outcome

• Published in: Brain research 1995-09, Vol.691 (1), p.76-82
• Main Authors: Çolak, Ahmet, Clay Goodman, J., Chen, Shu-Hsia, Woo, Savio L.C., Grossman, Robert G., David Shine, H.
• Format: Article
• Language: English
• Subjects: Adenovirus; Animal tumors. Experimental tumors; Animals; Antiviral Agents - pharmacology; beta-Galactosidase - genetics; Biological and medical sciences; Experimental nervous system tumors; Female; Ganciclovir - pharmacology; Gene therapy; Genetic Therapy; Genetic Vectors; Herpes simplex virus; Mastadenovirus - genetics; Medical sciences; Neoplasm Transplantation; Rats; Rats, Inbred F344; Simplexvirus - genetics; Spinal Cord Neoplasms - pathology; Spinal Cord Neoplasms - therapy; Spinal cord tumor; Survival Rate; Thymidine kinase; Thymidine Kinase - genetics; Treatment Outcome; Tumors
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00616-X

We evaluated the efficacy of adenoviral-mediated gene therapy of experimental spinal cord tumors and the functional outcome after this treatment. Spinal cord tumors were generated in the thoracic region of the spinal cord in Fischer 344 rats by stereotaxic intramedullary injection of 1 × 10 4 9L gliosarcoma cells. Seven days after tumor cell injection, a replication-defective adenoviral vector carrying the herpes simplex virus thymidine kinase gene (ADV-tk) or a control adenoviral vector carrying the β-galactosidase gene (ADV-βgal) was injected into the tumors. Beginning 12 h later the animals were treated with the antiviral drug ganciclovir (GCV; 50 mg/kg) or saline twice a day for 6 days. The neurological performance of the animals was assessed during and following treatment. Eighteen days after tumor cell injection, all of the control animals had paraplegia and large tumors. In contrast, no tumors were detected in animals treated with ADV-tk and GCV. In long-term studies, two of the 5 animals treated with ADV-tk and GCV remained tumor-free and remained neurologically intact at 6 months whereas all animals in the control groups became paraplegic within 18 days.