THERAPY OF MALIGNANT BRAIN-TUMORS BY INTRATUMORAL IMPLANTATION OF RETROVIRAL VECTOR-PRODUCING CELLS

Intratumoral implantation of murine cells modified to produce retrovir al vectors containing the herpes simplex virus-thymidine kinase (HSV-T K) gene induces regression of experimental brain tumors in rodents aft er ganciclovir (GCV) administration. We evaluated this approach in 15 patients with progressive growth of recurrent malignant brain tumors. Antitumor activity was detected in five of the smaller tumors (1.4 +/- 0.5 ml). In situ hybridization for HSV-TK demonstrated survival of ve ctor-producing cells (VPCs) at 7 days but indicated limited gene trans fer to tumors, suggesting that indirect, ''bystander,'' mechanisms pro vide local antitumor activity in human tumors. However, the response o f only very small tumors in which a high density of vector-producing c ells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clin ical utility is to be achieved with this approach.