Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses

Herpes simplex virus thymidine kinase (HSV tk) gene therapy combined with g anciclovir (GCV) medication is a potential new method for the treatment of malignant glioma, We have used both retrovirus-packaging cells (PA317/tk) a nd adenoviruses (Adv/tk) for gene therapy for malignant glioma, Retrovirus- packaging cells were used for eight tumors in seven patients and adenovirus es were used for seven tumors in seven patients. As a control group, seven tumors in seven patients were transduced with lacZ marker gene 4-5 days bef ore tumor resection, Safety and efficacy of the gene therapy were studied w ith clinical evaluation, blood and urine samples, MRI follow-up, and surviv al of the patients. Four patients with adenovirus injections had a signific ant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction. Frequency of epileptic seizures increased in two patients, No other adverse events possibly related to gene therapy were detected. In the retrovirus group, all treated gliomas showed progression by MRI at the 3-month time point, whereas three of the seven patients treated with Adv/t k remained stable (p < 0.05). Mean survival times for retrovirus, adenoviru s, and control groups were 7.4, 15.0, and 8.3 months, respectively. The dif ference in the survival times between the adenovirus and retrovirus groups was significant (p < 0.012). It is concluded that HSV tk gene therapy is sa fe and well tolerated. On the basis of these results further trials are jus tified, especially with adenovirus vectors.