Development of gene therapy for malignant brain tumor

恶性脑肿瘤基因治疗的进展

• 批准号: 04454358
• 负责人: YOSHIDA Jun
• 金额: $ 4.1万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454358/
• 关键词: gene therapy; brain tumor; interferon; liposome; monoclonal antibody; モノクローナル抗体

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.

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。

项目成果

Yoshida J, et al.: "Cytotoxicity of human β-interferon produced in human glioma cells transfected with its gene by means of liposomes" Biochem Int. 28. 1055-1061 (1992)

Yoshida J 等人：“通过脂质体转染其基因的人神经胶质瘤细胞中产生的人 β-干扰素的细胞毒性”Biochem Int. 28. 1055-1061 (1992)

Mizuno M., Yoshida J., et al.: "Lipsomal transfection of human gamma-interferon gene into glioma cells and adoptive immunotherapy using lymphokine-activated killer cells" J Neurosurg. 80. 510-514 (1994)

Mizuno M.、Yoshida J.等人：“将人γ-干扰素基因脂质体转染至神经胶质瘤细胞并使用淋巴因子激活的杀伤细胞进行过继免疫治疗”J Neurosurg。

Jun Yoshida: "Gene transfer with liposomes:Cytokine gene therapy for brain tumor" Cancer Chemothrapy:Challenges for the futher. (in press). (1994)

Jun Yoshida：“脂质体基因转移：脑肿瘤的细胞因子基因治疗”癌症化疗：未来的挑战。

Yoshida, J., et al.: "Antitumor effect of endogenous human beta-interferon on malignant glioma and augmentation of the effect by tumor necrosis factor-alpha" J Clin Biochem Nutr. 12. 153-160 (1992)

Yoshida, J. 等人：“内源性人 β-干扰素对恶性神经胶质瘤的抗肿瘤作用以及肿瘤坏死因子-α 增强作用”J Clin Biochem Nutr。

Takaoka T., Yoshida J., et al.: "Transfection-induced tumor necrosis factor-alpha increases the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells : Continuous expression of intercellular abhesion molecule-1 on the glioma c

Takaoka T.、Yoshida J. 等人：“转染诱导的肿瘤坏死因子-α 增加了人神经胶质瘤细胞对淋巴因子激活的杀伤细胞裂解的敏感性：神经胶质瘤 c 上细胞间粘附分子 1 的持续表达