Hashimura T, Ueda T, Hiura M, Yoshida O, Kawabata K, Watanabe Y, Takami M
Department of Urology, Faculty of Medicine, Kyoto University.
Hinyokika Kiyo. 1997 Nov;43(11):809-13.
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.
为了细胞因子基因疗法的临床应用，比较了全身给予干扰素-γ（IFN-γ）与体内直接将IFN-γ基因导入小鼠膀胱癌（MBT2）肿瘤的抗肿瘤效果。将MBT2细胞皮下接种到小鼠体内后，分别以10²、10³或10⁴单位的IFN-γ进行腹腔内（i.p.）或皮下（s.c.）注射。无论是腹腔内还是皮下注射IFN-γ均未导致肿瘤抑制，也未延长荷瘤小鼠的存活时间。还评估了通过逆转录病毒载体将IFN-γ基因体内直接导入MBT2肿瘤的效果。将MBT2细胞皮下接种到小鼠体内后，每天一次将含有IFN-γ基因的病毒培养上清液注射到同一肿瘤部位，共注射3天。在诱导IFN-γ基因的治疗组中，50%的小鼠未观察到肿瘤形成。治疗组的无瘤生存期和精算生存期明显长于对照组。这些结果表明了体内将IFN-γ基因直接导入肿瘤的可能性，并为开展针对人类膀胱癌的肿瘤细胞靶向IFN-γ基因疗法提供了鼓舞。
