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

Autor:	E. M. Oshiro, Linda M. Muul, E. Otto, Edward H. Oldfield, Yawen Chiang, R. M. Blaese, Zvi Ram, J. J. Viola, Zhifeng Long, Hetty L. DeVroom, Kenneth W. Culver, G. J. Mcgarrity, David A. Katz
Rok vydání:	1997
Předmět:	Ganciclovir Pathology medicine.medical_specialty Kinase Genetic enhancement General Medicine In situ hybridization Biology General Biochemistry Genetics and Molecular Biology Viral vector Transplantation Thymidine kinase Bystander effect medicine medicine.drug
Zdroj:	Nature Medicine. 3:1354-1361
ISSN:	1546-170X 1078-8956
Popis:	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:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::50b3296b83d18a478de5197e3afcc328 https://doi.org/10.1038/nm1297-1354 Zobrazit plný text záznamu