ADENOVIRUS-MEDIATED GENE-THERAPY FOR EXPERIMENTAL SPINAL-CORD TUMORS - TUMORICIDAL EFFICACY AND FUNCTIONAL OUTCOME

We evaluated the efficacy of adenoviral-mediated gene therapy of exper imental spinal cord tumors and the functional outcome after this treat ment. Spinal cord tumors were generated in the thoracic region of the spinal cord in Fischer 344 rats by stereotaxic intramedullary injectio n of 1 x 10(4) 9L gliosarcoma cells. Seven days after tumor cell injec tion, a replication-defective adenoviral vector carrying the herpes si mplex virus thymidine kinase gene (ADV-tk) or a control adenoviral vec tor carrying the P-galactosidase gene (ADV-beta-gal) was injected into the tumors. Beginning 12 h later the animals were treated with the an tiviral drug ganciclovir (GCV; 50 mg/kg) or saline twice a day for 6 d ays. The neurological performance of the animals was assessed during a nd following treatment. Eighteen days after tumor cell injection, all of the control animals had paraplegia and large tumors. In contrast, n o 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 remain ed tumor-free and remained neurologically intact at 6 months whereas a ll animals in the control groups became paraplegic within 18 days.