| Project/Area Number |
16K10777
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Takahashi Masamichi 国立研究開発法人国立がん研究センター, 中央病院, 医長 (10436454)
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| Co-Investigator(Kenkyū-buntansha) |
平岡 圭 北海道大学, 医学研究院, 客員研究員 (10719587)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 膠芽腫 / 遺伝子治療 / 放射線治療 / ウイルスベクター / 脳腫瘍 / レトロウイルス |
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| Outline of Final Research Achievements |
We investigated the therapeutic efficacy of the combination of our prodrug activating gene therapy system using retroviral replicating vector (RRV) and radiation therapy in experimental glioblastoma models. RRV efficiently spread to almost all the cells in commercially available glioblastoma cell lines including U87 and radioresistant U87EGFRvIII cells, whereas only 50% of the cells were infected in patient-derived glioblastoma stem-like cells. In stability assay, RRV was shown to safely maintain its ability of infection even after the irradiation. In survival study, mice harboring brain tumor with U87EGFRvIII cells were treated with combination of RRV prodrug system and radiation therapy showed significant elongated survival time compared to other groups. In conclusion, our RRV prodrug gene therapy system efficiently enhanced the anti-tumor effect of radiation therapy in experimental glioblastoma. Improved infection to glioblastoma stem-like cells should be further investigated.
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| Academic Significance and Societal Importance of the Research Achievements |
膠芽腫は最も予後不良の原発性悪性脳腫瘍の一つであり、新規治療法開発が切望されている。我々は本研究で、増殖型レトロウイルスベクター（RRV）を用いたプロドラッグシステムの放射線治療への増強効果について、膠芽腫細胞株を用いた基礎的研究、前臨床研究を行う事で検証した。その結果、RRVは膠芽腫細胞に広く感染して放射線照射を受けた後も安定してその感染能力を維持することが判明し、特にマウス脳腫瘍モデルにおいて効果的に放射線治療の抗腫瘍効果を増強させることが明らかとなった。これらの結果は現在論文として発表されるべく準備が進んでおり、将来的には膠芽腫患者を対象とした臨床応用が期待される。
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