Development of new therapy for brain tumors using recombinant oncolytic viruses
| Project/Area Number |
16390403
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The University of Tokyo |
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Principal Investigator |
TODO Tomoki The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (80272566)
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| Co-Investigator(Kenkyū-buntansha) |
INO Yasushi The University of Tokyo, Faculty of Medicine, Project Researcher, 医学部附属病院, 研究拠点形成特任教員 (50372371)
TANAKA Minoru The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (50332581)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2004: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Brain tumors / Oncolytic virus therapy / Herpes simplex virus type 1 / Viral vector / Antitumor immunity / 単純ヘルペスウイルスI型 |
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| Research Abstract |
Recombinant oncolytic herpes simplex virus type 1 (HSV-1) vectors are promising therapeutic agents for brain tumors. Insertion of therapeutic transgenes into the viral genome confers desired antitumor functions in addition to oncolytic activities. Because the efficacy of oncolytic HSV-1 also depends on the extent of antitumor immunity induction, immunomodulatory genes are particularly suited for "arming" oncolytic HSV-1 vectors. In order to circumvent time-consuming processes required with conventional homologous recombination techniques for creating "armed" oncolytic HSV-1 vectors, we used innovative construction systems utilizing bacterial artificial chromosome and recombinase-mediated recombinations. Triple gene-deleted HSV-1 vectors expressing immunostimulatory genes were generated and tested in HSV-1-susceptible AM mice bearing poorly-immunogenic Neuro2a (murine neuroblastoma) tumors. Intraneoplastic administration of "armed" oncolytic HSV-1 vectors expressing immunostimulatory genes resulted in significantly greater efficacy compared with unarmed control HSV-1, and led to growth inhibition of inoculated tumors as well as remote non-inoculated tumors. The antitumor effect on remote tumors was not due to viral spread but due to induction of systemic antitumor immunity requiring T lymphocytes. "Armed" oncolytic HSV-1 vectors could also suppress the growth of subcutaneous tumors when administered intravenously, whereas unarmed HSV-1 showed minimal effect. The results demonstrate that oncolytic HSV-1 therapy is a useful strategy for brain tumors, and "arming" with immunostimulatory genes can further improve the efficacy and usefulness of oncolytic HSV-1.
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Report
(4 results)
Research Products
(75 results)
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[Book] グリオーマ-病態と治療2006
Author(s)
藤堂具紀, 稲生靖, in田渕和雄(編)
Total Pages
274
Publisher
シュプリンガー・フェアラーク東京
Description
「研究成果報告書概要(和文)」より
Related Report
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