| Project/Area Number |
18H02641
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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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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
KANEKO SHIN 京都大学, iPS細胞研究所, 教授 (40361331)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | T細胞免疫治療 / iPS細胞 / 腫瘍浸潤T細胞 / 再生T細胞 / がんスフェロイド / 個別化再生T細胞治療 / T細胞免疫応 / 腫瘍浸潤リンパ球 / T細胞免疫応答 / T細胞分化 / がん免疫 / がんオルガノイド |
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| Outline of Final Research Achievements |
Tumor-infiltrating lymphocytes (TIL), which include tumor-specific T lymphocytes with frequency, are used for adoptive cell transfer therapy (ACT) in clinical practice. The optimization of TIL preparation has been investigated to reduce the senescence and increase the abundance of TIL, as both the quality and quantity of the transferred cells have great influence on the outcome of TIL-based ACT (TIL-ACT). Considering the effects of cell reprogramming on senescence, we expected that the anti-tumor effect could be enhanced by TIL regeneration. To confirm this hypothesis, we established tumor-specific TIL-derived iPS cells (TIL-iPSC) with human colorectal cancer specimens. T cells differentiated from TIL iPSC (TIL-iPS-T) retained not only intrinsic T cell functions and tumor specificity, but also exhibited improved proliferation capacity and additional killing activity. Moreover, less differentiated profiles and prolonged persistency were seen in TIL-iPS-T compared with primary cells.
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| Academic Significance and Societal Importance of the Research Achievements |
iPS細胞の最大の利点は、自らの多能性幹細胞をもって長期に機能する再生細胞をもちいたオーダーメード治療を実現できることである。その点からはいわゆるneoantigenを認識する腫瘍抗原特異的T細胞の分離と再生が技術的に可能であれば、誰でも自己の腫瘍を認識する再生T細胞治療の恩恵を受けられる可能性がでてくる。本プラットフォーム研究を通じて、患者検体を用いたTILの再生と自家腫瘍スフェロイドに対するエフェクター機能のPOCを示すことができたことから、今後はより治療効果を向上させるための個別研究へと発展することが期待される。またその結果、新しい個別化免疫治療法の実現可能性が高まると考える。
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