2001 Fiscal Year Final Research Report Summary
Development of tumor specific expression by replication defective HSV-1 vector against malignant glioma
| Project/Area Number |
12671357
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
MORIUCHI Shusuke Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90322180)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMINE Toshiki Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00201046)
MARUNO Motohiko Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (10263287)
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| Project Period (FY) |
2000 – 2001
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| Keywords | glioblastoma / HSV-1 / gene therapy / tumor specific promoter / E2F-1 / virus vector / malignant glioma |
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| Research Abstract |
We have been studying gene therapy against malignant glioma by replication defective HSV-1 vector. TH/TNF, which coexpresses TNF-alpha and HSV-TK, have been developed. We have confirmed that TNF-alpha made by TH/TNF enhanced the toxicity of HSV-TK/GCV suicide gene therapy in vitro and in vivo. In addition with this experiment, gamma knife radiation therapy could enhance the cytotoxicity effectively and 90% of tumor bearing mice could be prolonged survival more than 4 times than control groups. This time, we have developed replication defective HSV-1 vector (SEP4) which coexpressed GFP and ICP4 under the control of tumor specific promoter, E2F-1. SEP4 has mutations in ICP4 and replication defective in glioma cells. When SEP4 infects tumor cells or glioma cells, the E2F-1 tumor specific promoter can drive the expression of GFP and ICP4, and SEP4 can replicate in the tumor cells with the expression of ICP4. We confirmed the expression of GFP in the human glioblastoma cells and not expressed in the primary cultured neurons or glias. We also confirmed glioma specific replication of SEP4 in U-87MG human glioblastoma cells.
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