Development of cell therapy for patients with tumors utilizing allogeneic stealth T cells
| Project/Area Number |
18H02872
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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 55010:General surgery and pediatric surgery-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
IKEDA Hiroaki 長崎大学, 医歯薬学総合研究科(医学系), 教授 (40374673)
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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 |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
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| Keywords | 細胞療法 / 遺伝子治療 / がん / 移植 / 非自己細胞 / TCR / MHC / siRNA / 腫瘍 |
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| Outline of Final Research Achievements |
In this study, we aimed to develop cell therapy that utilize allogeneic cells for cancer immunotherapy as well as transplantation medicine. Using CRISPER/Cas 9 system or novel retrovirus vector with siRNA, we successfully silenced MHC class I and enforced the expression of HLA-E in allogeneic T cells, resulting in effective escape from the attack from CD8+ T cells as well as NK cells. These T cells were suggested to be highly stealth allogeneic T cells for cancer immunotherapy. Similar results were observed when we utilized a hepatocyte cell line. These data suggests that our technology here is a promising strategy for transplantation medicine with reduced immunosuppressive drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、がんのT細胞療法において非自己のリンパ球を用いる可能性が示された。このことにより、タイムリーに安価で有効性が高い「オフザシェルフ」のT細胞療法が提供可能になることを意味し、多くのがん患者が有効ながん免疫療法の恩恵を受ける可能性を示している。このことは現在有効な治療法が確立していないがん患者の救済になると共に、医療費を抑え医療経済に貢献することが期待される。また、本研究は移植医療においては免疫抑制剤の使用を減らしながら移植片の拒絶を防ぐ可能性を示しており、本研究の技術を応用することによって移植を受ける患者が長期に健康を維持することが期待される。
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Report
(4 results)
Research Products
(63 results)
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[Journal Article] Dabrafenib and trametinib therapy in an elderly patient with non-small cell lung cancer harboring the BRAF V600E mutation.2020
Author(s)
Dotsu Y, Fukuda M, Honda N, Gyotoku H, Kohno Y, Suyama T, Umeyama Y, Taniguchi H, Takemoto S, Yamaguchi H, Miyazaki T, Sakamoto N, Obase Y, Ikeda H, Ashizawa K, Mukae H.
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Journal Title
Thorac Cancer
Volume: 12
Issue: 2
Pages: 272-276
DOI
Related Report
Peer Reviewed / Open Access
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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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[Journal Article] Antitumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination.2018
Author(s)
Akahori Y, Wang L, Yoneyama M, Seo N, Okumura S, Miyahara Y, Amaishi Y, Okamoto S, Mineno J, Ikeda H, Maki T, Fujiwara H, Akatsuka Y, Kato T, Shiku H.
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Journal Title
Blood. 2018 Sep 13;132(11):
Volume: 132
Issue: 11
Pages: 1134-1145
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic value of MAGEA4 in primary lung cancer depends on subcellular localization and p53 status.2018
Author(s)
Fujiwara-Kuroda A, Kato T, Abiko T, Tsuchikawa T, Kyogoku N, Ichinokawa M, Tanaka K, Noji T, Hida Y, Kaga K, Matsui Y, Ikeda H, Kageyama S, Shiku H, Hirano S
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Journal Title
International Journal of Oncology
Volume: 53
Pages: 713-724
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical Implications of CD4+CD25+Foxp3+Regulatory T Cell Frequencies After CHP-MAGE-A4 Cancer Vaccination2018
Author(s)
Wada M, Tsuchikawa T, Kyogoku N, Abiko T, Miyauchi K, Takeuchi S, Kuwatani T, Shichinohe T, Miyahara Y, Kageyama S, Ikeda H, Shiku H, Hirano S.
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Journal Title
Anticancer Research
Volume: 38
Issue: 3
Pages: 1435-1444
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Anti-tumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination2018
Author(s)
赤堀 泰, 王 立楠, 米山 元裕, 瀬尾 尚宏, 奥村 悟司, 宮原 慶裕, 天石 泰典, 岡本 幸子, 峯野 純一, 池田 裕明, 真木 健裕, 藤原 弘, 赤塚 美樹, 加藤 琢磨, 珠玖 洋
Organizer
第22回日本がん免疫学会総会
Related Report
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