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Development of gene therapy for malignant melanoma with transfection of human IFN-β gene

转染人IFN-β基因开发恶性黑色素瘤基因治疗

基本信息

批准号：
11557064
负责人：
SAIDA Toshiaki
金额：
$ 8.45万
依托单位：
Shinshu University School of Nedicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557064/
关键词：
Malignant melanoma Gene therapy Interferon-β Liposome

项目摘要

The purpose of this project is to develop a new gene therapy for patients with advanced malignant melanoma, which is highly resistant to any conventional therapies. In our previous study, we found that malignant melanoma transfected with interferon-β( IFN-β ) gene by means of cationic multilamellar liposomes expressed the gene and secreted IFN-β. Moreover, human melanoma nodules transplanted to nude mice were eradicated completely with 6 times injection of IFN-β gene ( 3ug DNA/time ). This year, we have investigated mechanisms of effect of this gene therapy. We have found transfection of IFN-β gene induces apoptosis of melanoma cells. In addition, in experiments in the murine B16 melanoma system, we have found NK cells play an important role in the growth inhibition ofmelanoma nodules in C57BL/6 mice. Furthermore, we have confirmed repeated treatment with the cationic liposome containing IFN-β gene increases tranfection efficiency of the gene.Based on the data obtained in studies in this year along with those performed in the previous 2 years, we consider we have almost completely finished preparation for the clinical study. We have now applied clinical trial of this gene therapy to the committees of our medical school in order to start the clinical study of the gene therapy for patients with advanced melanoma.

该项目的目的是为晚期恶性黑色素瘤患者开发一种新的基因治疗方法，该患者对任何常规治疗都具有高度抵抗性。我们在前期的研究中发现，用阳离子多层脂质体介导的β-干扰素（IFN-β）基因转染恶性黑色素瘤细胞后，能表达IFN-β基因并分泌IFN-β。3 μ gDNA/次注射IFN-β基因6次可完全清除裸鼠移植瘤。今年，我们研究了这种基因治疗的作用机制。我们发现IFN-β基因转染可诱导黑色素瘤细胞凋亡。此外，在小鼠B16黑色素瘤系统的实验中，我们发现NK细胞在抑制C57 BL/6小鼠黑色素瘤结节的生长中起重要作用。此外，我们已经证实，用含有IFN-β基因的阳离子脂质体重复处理可以提高基因的转染效率，根据沿着今年的研究和前两年的研究获得的数据，我们认为我们已经基本完成了临床研究的准备工作。我们现在已经向我们医学院的委员会申请了这种基因治疗的临床试验，以便开始晚期黑色素瘤患者的基因治疗的临床研究。