Development of brain tumor-penetrant protein delivery system realizing immunotherapy of malignant brain tumor
| Project/Area Number |
18H04170
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 90:Biomedical engineering and related fields
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
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Principal Investigator |
Kataoka Kazunori 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, センター長 (00130245)
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| Co-Investigator(Kenkyū-buntansha) |
Cabral Horacio 東京大学, 大学院工学系研究科(工学部), 准教授 (10533911)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥44,590,000 (Direct Cost: ¥34,300,000、Indirect Cost: ¥10,290,000)
Fiscal Year 2020: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2019: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2018: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
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| Keywords | ドラッグデリバリーシステム / がん免疫療法 / 脳腫瘍 / 高分子ミセル / タンパク質デリバリー / 免疫チェックポイント阻害剤 / 血液脳腫瘍関門 / 還元環境応答性 / リガンド分子 |
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| Outline of Final Research Achievements |
Glioblastomas construct the blood-brain tumor barrier (BBTB) in their blood vessels, which impairs the efficacy of immune checkpoint inhibitors. In this study, we developed nanocarriers that can efficiently and selectively deliver immune checkpoint inhibitors to glioblastoma by passing BBTB. As an immune checkpoint inhibitor, we used anti-PD-L1 antibody. Two types of nanocarriers have been developed: (1) nanocarriers based on polymeric micelles that encapsulate antigen-binding fragments of anti-PD-L1 antibody and (2) nanocarriers prepared by modifying whole anti-PD-L1 antibodies with hydrophilic polymers. Both types of nanocarriers released immune checkpoint inhibitors in response to reducing or weakly acidic conditions relevant to microenvironment in glioblastoma. In particular, the latter type of nanocarriers demonstrated a potent anticancer effect against glioblastoma while avoiding immune-related adverse events.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性脳腫瘍のうち悪性度が特に高いことで知られる膠芽腫は、有効な治療法が存在せず、余命の中央値は16か月未満と悲惨な状況にある。様々ながんに対して顕著な有効性を示す免疫チェックポイント阻害剤も膠芽腫には効果がない。この一つの理由として、膠芽腫内血管の内皮細胞が血液脳腫瘍関門を形成して物質輸送を著しく制限していることが挙げられる。本研究は、免疫チェックポイント阻害剤を膠芽腫内に効率的に送り込む技術の開発に成功しただけでなく、膠芽腫内の微小環境に応じて免疫チェックポイント阻害剤を放出する機能を付加することで、臨床で問題となっている免疫関連毒性の低減にも成功した極めて意義の大きいものである。
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Report
(2 results)
Research Products
(60 results)
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[Journal Article] Glucose-linked sub-50-nm unimer polyion complex-assembled gold nanoparticles for targeted siRNA delivery to glucose transporter 1-overexpressing breast cancer stem-like cells.2019
Author(s)
Y. Yi, H. J. Kim, M. Zheng, P. Mi, M. Naito, B. S. Kim, H. S. Min, K. Hayashi, F. Perche, K. Toh, X. Liu, Y. Mochida, H. Kinoh, H. Cabral, K. Miyata, K. Kataoka
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Journal Title
J. Control. Release
Volume: 295
Pages: 268-277
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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