Personalized cancer immunotherapy of gastrointestinal tumors based on identification of neoantigens and reverting of immunosuppression
| Project/Area Number |
18K19584
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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 | 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) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | がん免疫療法 / 個別化医療 / ネオアンチゲン / 免疫抑制機構 / 個別化治療 / 免疫抑制 / がん免疫編集 |
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| Outline of Final Research Achievements |
In this study, we aimed to develop the highly personalized cancer immunotherapy targeting neoantigen. We found that BALB/c mouse-derived one colorectal cell line and two fibrosarcoma cell lines possessed 200~300 nonsynonymous mutations. Utilizing these cell lines, we demonstrated that anti-tumor effect of neoantigen-targeted adoptive T cell therapy was enhanced by the vaccination targeting macrophages in tumor. Moreover, we demonstrated the the adoptive T cell therapy targeting neoantigen was enhanced by a novel substance X that activated NF-kB pathway in neoantigen-specific T cells.
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| Academic Significance and Societal Importance of the Research Achievements |
真に有効ながん免疫療法は各がん患者に合わせて個別化デザインされる必要がある。本研究において我々はマウスの大腸癌、線維肉腫の系を用いて、各患者に個別の標的であるネオアンチゲンを狙ったT細胞輸注療法が腫瘍内マクロファージを標的としたがんワクチン療法によって増強されることを示した。また新規化合物XがT細胞のNF-kB経路を活性化することによって、ネオアンチゲンを標的としたT細胞輸注療法を増強することを見出した。これらの成果は現在有効な治療法の無いがん患者にとって個別のネオアンチゲンを標的とした新規で有効な個別化がん免疫療法を届けることに貢献すると期待される。
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Report
(4 results)
Research Products
(61 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
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