[Gene therapy by in vivo interferon-gamma gene transfer to murine bladder tumor].
For the clinical application of the cytokine gene therapy, the antitumor effects of systemic administration of Interferon-gamma (IFN-gamma) and those of in vivo direct IFN-gamma gene transfer to the tumors of mouse bladder carcinoma (MBT2) were compared. After the subcutaneous inoculation of MBT2 cells into mice, 10(2), 10(3) or 10(4) units of IFN-gamma were injected intraperitoneally (i.p.) or subcutaneously (s.c.). Neither i.p. nor s.c. injection of IFN-gamma resulted in tumor suppression or prolonged the survival time of tumor-bearing mice. The effect of in vivo direct IFN-gamma gene transfer by a retrovirus vector to MBT2 tumors was also evaluated. After the subcutaneous inoculation of MBT2 cells into mice, a virus culture supernatant containing IFN-gamma gene was injected into the same tumor site once a day for 3 days. In 50% of the mice in the treatment groups with IFN-gamma gene induction, no tumor formation was observed. Tumor-free survival and actuarial survival in the treatment groups were significantly longer than those in the control group. These results showed the possibility of in vivo direct IFN-gamma gene transfer into tumors and were encouraging for the execution of tumor cell-targeted IFN-gamma gene therapy against human bladder cancer.
Hashimura
T
T
Department of Urology, Faculty of Medicine, Kyoto University.
Ueda
T
T
Hiura
M
M
Yoshida
O
O
Kawabata
K
K
Watanabe
Y
Y
Takami
M
M
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
D007371:Interferon-gamma