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GENE THERAPY FOR MALIGNANT BRAIN TUMORS USING HSV/EBV HYBRID AMPLICONS.

使用 HSV/EBV 混合扩增子对恶性脑肿瘤进行基因治疗。

基本信息

批准号：
14370433
负责人：
TAMIYA Takashi
金额：
$ 6.72万
依托单位：
KAGAWA UNIVERSITY(FACULTY OF MEDICINE) (2003)Okayama University (2002)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370433/
关键词：
gene therapy gene expression glioma Herpes virus vector EB virus vector Adenovirus vector Cytosin deaminase gene transferrin receptor MRI

项目摘要

Previously, we evaluated the therapeutic efficacy of the virus-mediated transduction of the chemosensitivity genes and prodrugs for malignant gliomas such as 5-fluorocytosine (5-FC)/cytosine deaminase (CD) gene therapy.Firstly, we investigated the ability of radiation therapy to enhance 5-fluorocytosine (5-FC)/cytosine deaminase (CD) plus uracil phosphoribosyltransferase (UPRT) gene therapy in malignant gliomas. This combination therapy may be feasible for the treatment of gliomas, although the radiation dose and area should be reduced in order to prevent side effects (Cancer Gene Therapy 9 : 840-845, 2002).Secondly, we examined the induction of apoptosis and the role of caspases in 5-FC/CD gene therapy using human malignant glioma cells. These results indicate that 5-FC/CD gene therapy induces apoptosis in human malignant glioma cells and that the apoptotic cell death is mediated by the activation of mitochondrial caspase cascades involving caspases 3 and 9 (J of Neuro-Oncology 66 : 117-127, 2004).Recently, we are making new HSV/EB hybrid-based amplicon vector system for transgene delivery and developing the use MRI for in vivo imaging of transgene expression employing engineered transferrin receptor.

在此之前，我们评估了病毒介导的转导恶性胶质瘤化疗敏感基因和前药的治疗效果，如5-氟胞嘧啶（5-FC）/胞嘧啶脱氨酶（CD）基因治疗。首先，我们研究了放射治疗增强5-氟胞嘧啶（5-FC）/胞嘧啶脱氨酶（CD）联合尿嘧啶磷酸核糖转移酶（UPRT）基因治疗恶性胶质瘤的能力。这种联合疗法对于治疗神经胶质瘤可能是可行的，尽管为了防止副作用，应该减少辐射剂量和面积（Cancer Gene Therapy 9：840-845，2002）。其次，我们使用人恶性神经胶质瘤细胞检测了5-FC/CD基因疗法中凋亡的诱导和半胱天冬酶的作用。这些结果表明，5-FC/CD基因治疗诱导人恶性胶质瘤细胞凋亡，凋亡性细胞死亡是通过激活线粒体caspase级联介导的，涉及caspase 3和9（神经肿瘤学杂志66：117-127，2004）。最近，我们正在制造用于转基因递送的新的基于HSV/EB杂交的扩增子载体系统，并开发MRI用于采用工程化转铁蛋白受体的转基因表达的体内成像的用途。