膀胱癌細胞へのin vivoにおけるInterferon-γ遺伝子導入による遺伝子治療

Abstract

遺伝子治療の基礎的実験として, マウス膀胱癌細胞株MBT2の移植腫瘍に対して, IFN-γの全身投与と, 腫瘍へのIFN-γ遺伝子導入により抗腫瘍効果が異なるかを検討した. 1)マウス膀胱癌MBT2移植腫瘍に対してIFN-γを皮下注或いは腹腔内投与した.腫瘍形成の抑制, 生存期間の延長は認められず, IFN-γの全身投与の有意な抗腫瘍効果はなかった. 2)マウス膀胱癌MBT2移植腫瘍に対してIFN-γ遺伝子を腫瘍に導入した.腫瘍形成の抑制, 生存期間の延長が認められ, IFN-γ遺伝子の腫瘍細胞への導入により有意な抗腫瘍効果が認められた

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.