| Project/Area Number |
16H05387
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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 |
Radiation science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Tsuboi Koji 筑波大学, 医学医療系, 教授 (90188615)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 敦夫 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (30356480)
榮 武二 筑波大学, 医学医療系, 教授 (60162278)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 放射線治療 / ヒストン脱アセチル化酵素阻害剤 / メソポーラスシリカ / がん免疫療法 / アブスコパル効果 / 放射線増感効果 / がん陽子線治療 / 免疫原性細胞死 / がん特異的免疫応答 / ナノ粒子アジュバント / 放射照射治療 / SAHA / 陽子線治療 / がん免疫応答 / ナノ粒子アジュバンド / 放照射線治療 / がん / 陽子線 / HDAC阻害剤 |
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| Outline of Final Research Achievements |
We examined how a HDAC inhibitor “suberovlanilide hydroxyamic acid (SAHA) sensitizes the radiation effect on normal and tumor cells. As a result, SAHA inhibited the DNA homologous recombination repair, and increased the yield of DNA double strand breaks. These radio-sensitizing effects were significantly greater in tumor cells than in normal cells, indicating that SAHA may be able to sensitize cancer cells selectively after irradiation. We also examined whether a novel immune-adjuvant “mesoporous silica (MS)” nanoparticles could promote local tumor control and induce the abscopal effect using a mouse subcutaneous tumor model. As a result, intratumoral administration of MS after X-ray irradiation activated the systemic tumor-specific immune response, improving the local tumor control rate and enhancing the abscopal effect in the brain. In addition, it was confirmed that MS was not toxic in subcutaneous administration.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒストン脱アセチル化酵素阻害剤SAHAは腫瘍細胞と正常細胞のDNA修復メカニズムの違いに基づく腫瘍選択的な増感効果が期待でき用法の拡大により固形悪性腫瘍に対する新たな放射線増感剤として期待できる。また、メソポーラスシリカナノ粒子は放射線照射後に放出される腫瘍溶解成分を吸着し全身的な腫瘍免疫賦活効果を賦活することから放射線治療後の再発や遠隔転移を防ぐことが可能であり、毒性も低く取り扱いが容易であることからその臨床応用が期待される。局所的放射線療法と全身的な免疫療法をお互いに補完しつつそれぞれの特徴を生かすことにより、原理的には腫瘍の種類を問わず適用可能な「放射線・複合免疫療法」が実現できる。
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