Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells.
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.
Ram
Z
Z
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.
Culver
K W
KW
Oshiro
E M
EM
Viola
J J
JJ
DeVroom
H L
HL
Otto
E
E
Long
Z
Z
Chiang
Y
Y
McGarrity
G J
GJ
Muul
L M
LM
Katz
D
D
Blaese
R M
RM
Oldfield
E H
EH
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000628:therapy*; D017690:Cell Transplantation; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D012190:Retroviridae / Q000235:genetics*; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D013937:Thymidine Kinase; D015774:Ganciclovir