T cell optimization for effective CAR-T cell therapy to refractory esophageal cancer
| Project/Area Number |
19K22655
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Mie University |
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Principal Investigator |
Kageyama Shinichi 三重大学, 医学系研究科, リサーチアソシエイト (80194695)
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| Co-Investigator(Kenkyū-buntansha) |
宮原 慶裕 三重大学, 医学系研究科, 産学官連携講座教授 (10582083)
加藤 琢磨 三重大学, 医学系研究科, 准教授 (60224515)
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| Project Period (FY) |
2019-06-28 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 食道癌 / がん免疫療法 / T細胞治療 / 遺伝子改変T細胞輸注療法 / CAR-T療法 / TCR遺伝子導入T細胞 / CAR-T細胞 / MAGE-A4 |
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| Outline of Research at the Start |
固形腫瘍（食道癌）に有効なMAGE-A4新規CAR-T療法に用いるT細胞の最適な調製法、選択法、複合的治療（T細胞の代謝改善薬との併用）のためのrationale構築とin vivoモデルによるPOC取得をする。
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| Outline of Final Research Achievements |
To develop a CAR-T therapy for refractory esophageal cancer, we comprehensively analyzed the phenotype, immune function, and transcriptome (including gene expression analysis related to glucose and fat metabolism) of TCR-gene transduced T cells infused in clinical trials to identify factors associated with in vivo persistence and clinical efficacy.
Factors associated with in vivo persistence and clinical efficacy were explored, and subpopulations selected. The CRS (cytokine release syndrome) pathogenesis involved host-derived cytokines after TCR-T infusion and was significantly related to the differentiation traits of infused TCR-T (manufactured T cells). It was also inferred that TCR-T traits (CD39, CD244) and clinical response (CRS, tumor shrinkage) were involved after infusion.
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| Academic Significance and Societal Importance of the Research Achievements |
転移再発食道癌に対する有効な治療手段がないのが現状であるが、近年免疫療法への期待が高い。本研究はT細胞療法の基盤研究であり、新しいCAR-T細胞療法の臨床開発のための基盤研究である。CAR-T細胞療法ではサイトカイン放出症候群を避けながら有効性を向上させることが重要であり、本研究では臨床反応に関連する因子が特定された。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors.2020
Author(s)
Ishihara M, Tono Y, Miyahara Y, Muraoka D, Harada N, Kageyama S, Sasaki T, Hori Y, Soga N, Uchida K, Shiraishi T, Sato E, Kanda H, Mizuno T, Webster GA, Ikeda H, Katayama N, Sugimura Y, Shiku H.
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Journal Title
Cancer Immunol Immunother
Volume: 69
Issue: 4
Pages: 663-675
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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