Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells.

Autor: Ram Z; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA., Culver KW, Oshiro EM, Viola JJ, DeVroom HL, Otto E, Long Z, Chiang Y, McGarrity GJ, Muul LM, Katz D, Blaese RM, Oldfield EH
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 1997 Dec; Vol. 3 (12), pp. 1354-61.
DOI: 10.1038/nm1297-1354
Abstrakt: Intratumoral implantation of murine cells modified to produce retroviral vectors containing the herpes simplex virus-thymidine kinase (HSV-TK) gene induces regression of experimental brain tumors in rodents after 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 vector-producing cells (VPCs) at 7 days but indicated limited gene transfer to tumors, suggesting that indirect, "bystander," mechanisms provide local antitumor activity in human tumors. However, the response of only very small tumors in which a high density of vector-producing cells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clinical utility is to be achieved with this approach.
Databáze: MEDLINE