Development of gene therapy for malignant brain tumor

我们的研究方向是利用DNA/免疫脂质体（单克隆抗体偶联阳离子脂质体）选择性地将细胞因子基因导入肿瘤细胞。我们在目前的研究工作中证实，通过使用在裸鼠脑中产生的人胶质瘤，转染诱导的HuIFN-β的抗肿瘤作用。我们将人脑胶质瘤细胞注入大脑半球。人类神经胶质瘤在老鼠大脑中生长，它们都形成了一个巨大的脑瘤。为了评价抗肿瘤效果，我们将包封有pSV 2 IFN-β的脂质体注射到脑内生长的肿瘤中，每隔一天注射一次，共注射六次。我们在移植后的不同时间开始治疗，并在第31天将所有动物处死，结果表明，当将包封有pSV 2 IFN-β的脂质体反复注射到肿瘤中时，移植的胶质瘤完全消失。移植后3天开始给药，裸鼠移植瘤完全消失率为100%，第7天和第9天分别为5/7（71%）和2/7（29%）。因此，通过使用DNA/免疫脂质体，注意到转染诱导的HuIFN-β的抗肿瘤作用增加。

Our approach developing gene therapy to malignant glioma is selectively transfer of cytokine gene into the tumor cells by means of DNA/immunoliposomes (monoclonal antibody coupled cationic liposomes). We confim in the present research work, the anti-tumor effect of transfection-induced HuIFN-beta by the use of human glioma produced in the brain of nude mice. We injected humanglioma cells into the cerebral hemisphere. The human gliomas grew in the mouse brain and they all made a huge brain tumor. For the evaluation of anti-tumor effect, we injected liposomes with entrapped pSV2IFN-beta into the tumor growing tn the brain once every second day for six times. We started the treatment at different days after the transplantation and sacrified all animals at 31st day, and it has been demonstrated that the transplanted glioma disappasred completely when the liposomes with entrapped pSV2IFN-beta was injected repeatedly into the tumor. The complete disappearance of the transplanted glioma was seen in 100% of nude mice if the treatment was started until 3 days after transplantation and when it was started at 7 days or 9 days, the tumor-free ratio was 5/7 (71%) or 2/7 (29%) respectively. Futhermore, the anti-tumor effect of transfection-induced HuIFN-beta was noted to be increased by using DNA/immunoliposomes.