New approaches to transfer genetic material into tumor and normal central nervous system (CNS) tissue is being explored. The mechanisms involved in effecting antitumor activity using the suicide gene transfer approach are investigated. Normal and tumor vasculature, choroid plexus epithelium, and than normal CNS structures are being targeted. New viral vectors, including adenoviruses, are being evaluated for potential therapeutic approaches. A clinical trial for treating patients with recurrent malignant brain tumors with a retroviral vector containing the gene for Herpes simplex thymidine kinase (HsTk) and intravenous ganciclovir (GCV) was completed. The results indicate that 1) the producer-cell approach can be used successfully without toxicity in human brain tumors, 2) antitumor activity occurs in some patients, 3) limited gene transfer into tumor cells occurs with this approach for delivery and distribution, and 4) """"""""bystander effects"""""""" probably underlie the antitumor activity. The results highlight the need for improved methods of drug delivery and distribution in solid tissues. They also suggest that with improvements in gene delivery and development of techniques to select patients with tumors that are more likely to respond, this approach may have clinical utility.
