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

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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.