Adeno-associated virus vector containing the herpes simplex virus thymidine kinase gene causes complete regression of intracerebrally implanted human gliomas in mice, in conjunction with ganciclovir administration.
Adeno-associated virus (AAV) has attracted considerable interest as a potential vector for gene therapy because of its wide host range, high transduction efficiency, and lack of cytopathogenicity. In this experiment, we evaluated the efficacy of AAV vector containing the herpes simplex virus thymidine kinase (HSV-tk) gene on human gliomas transplanted into the brain of nude mice. Complete regression of the tumors was observed after multiple AAV-tk injections followed by intraperitoneal ganciclovir (GCV) administration, and the survival of mice treated with AAV-tk vector and GCV administration was markedly prolonged. These results suggest that AAV-tk vectors may be useful for gene therapy against malignant gliomas in humans.
Mizuno
M
M
Department of Neurosurgery, Nagoya University School of Medicine.
Yoshida
J
J
Colosi
P
P
Kurtzman
G
G
D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D015996:Survival Rate; D013937:Thymidine Kinase / Q000008:administration & dosage / Q000235:genetics*; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D015774:Ganciclovir