Comprehensive analysis of cancer-specific antigens recognized by tumor-infiltrating T cells
Project/Area Number |
19H03522
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Japanese Foundation for Cancer Research |
Principal Investigator |
KIYOTANI Kazuma 公益財団法人がん研究会, がんプレシジョン医療研究センター 免疫ゲノム医療開発プロジェクト, 主任研究員 (30433642)
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Co-Investigator(Kenkyū-buntansha) |
黒田 大祐 東京大学, 大学院工学系研究科(工学部), 講師 (60756732)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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Keywords | 腫瘍浸潤T細胞 / ネオアンチゲン / T細胞受容体 / ネオ抗原 |
Outline of Research at the Start |
がん局所に浸潤したT細胞(腫瘍浸潤T細胞) はsomatic変異由来のneoantigenなど様々ながん特異的抗原を認識し、抗腫瘍効果を示す。本研究では、腫瘍浸潤T細胞がneoantigenを含めどのような抗原を認識しているかを網羅的に解析し、その抗原とT細胞受容体を予測するシステムを開発することを目的としている。新鮮手術検体を用いて、1) 腫瘍浸潤T細胞レパトア解析によるがん特異的T細胞の同定、2) タンパク質の立体構造に基づく分子シミュレーションと機械学習によるがん特異的T細胞の予測、の二つの項目について解析する。
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Outline of Final Research Achievements |
The purpose of this study was to screen antigens of tumor-infiltrating T cells, and establish prediction system for antigen-TCR interactions. We collected fresh surgical tissues of colorectal cancer and isolated tumor-infiltrating T cells and patient-derived cancer cells (PDCs). We established the system to enrich tumor-reactive T cells by co-culture of tumor-infiltrating T cells and PDCs, and obtained TCRs from tumor-reactive T cells. Using TCR-engineered T cells, we confirmed that TCRs from tumor-reactive T cells are actually tumor-reactive, but not always neoantigen-reactive.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、腫瘍浸潤T細胞と患者由来がん細胞の共培養により、腫瘍反応性T細胞を増殖できる系を開発した。この方法は、腫瘍内の腫瘍反応性T細胞の同定、さらには腫瘍反応性T細胞を用いた治療法開発にもつながると考えられる。さらに、T細胞が認識する抗原の網羅的な探索系の開発も進めており、この系は様々な用途に利用可能であると考えている。
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] Perioperative circulating tumor DNA enables the identification of patients with poor prognosis in upper tract urothelial carcinoma2022
Author(s)
Nakano K, Koh Y, Yamamichi G, Yumiba S, Tomiyama E, Matsushita M, Hayashi Y, Wang C, Ishizuya Y, Yamamoto Y, Kato T, Hatano K, Kawashima A, Ujike T, Fujita K, Kiyotani K, Katayama K, Yamaguchi R, Imoto S, Imamura R, Nonomura N, Uemura M
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Journal Title
Cancer Science
Volume: -
Issue: 5
Pages: 1830-1842
DOI
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Peer Reviewed
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[Journal Article] Current advances in biopharmaceutical informatics: guidelines, impact and challenges in the computational developability assessment of antibody therapeutics2022
Author(s)
Khetan R, Curtis R, Deane CM, Hadsund JT, Kar U, Krawczyk K, Kuroda D, Robinson SA, Sormanni P, Tsumoto K, Warwicker J, Martin ACR.
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Journal Title
mAbs
Volume: 14
Issue: 1
Pages: 2020082-2020082
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Efficacy of intranodal neoantigen peptide-pulsed dendritic cell vaccine monotherapy in patients for advanced solid tumors; retrospective analysis.2021
Author(s)
Morisaki T, Morisaki T, Kubo M, Onishi H, Hirano T, Morisaki S, Eto M, Monji K, Takeuchi A, Nakagawa S, Tanaka H, Koya N, Umebayashi M, Tsujimura K, Yew PY, Yoshimura S, Kiyotani K, Nakamura Y
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Journal Title
Anticancer Res
Volume: 41(8)
Issue: 8
Pages: 4101-4115
DOI
Related Report
Peer Reviewed
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[Journal Article] Neoantigens elicit T cell responses in breast cancer2021
Author(s)
Morisaki T, Kubo M, Umebayashi M, Yew PY, Yoshimura S, Park JH, Kiyotani K, Kai M, Yamada M, Oda Y, Nakamura Y, Morisaki T, Nakamura M.
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Journal Title
Scientific Reports
Volume: 11
Issue: 1
Pages: 13590-13590
DOI
Related Report
Peer Reviewed
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[Journal Article] Generation of neoantigen-specific T cells for adoptive cell transfer for treating head and neck squamous cell carcinoma2021
Author(s)
Wei T, Leisegang M, Xia M, Kiyotani K, Li N, Zeng C, Deng C, Jiang J, Harada M, Agrawal N, Li L, Qi H, Nakamura Y, Ren L.
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Journal Title
OncoImmunology
Volume: 10
Issue: 1
Pages: 1929726-1929726
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma2021
Author(s)
Kato T, Kiyotani K, Tomiyama E, Koh Y, Matsushita M, Hayashi Y, Nakano K, Ishizuya Y, Wang C, Hatano K, Kawashima A, Ujike T, Fujita K, Nonomura N, Uemura M.
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Journal Title
OncoImmunology
Volume: 10
Issue: 1
Pages: 1862948-1862948
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Immunogenomic landscape of gynecologic carcinosarcoma2021
Author(s)
Gotoh Osamu、Kiyotani Kazuma、Chiba Tomohiro、Sugiyama Yuko、Takazawa Yutaka、Nemoto Kensaku、Kato Kazuyoshi、Tanaka Norio、Nomura Hidetaka、Hasegawa Kosei、Fujiwara Keiichi、Takamatsu Shiro、Matsumura Noriomi、Noda Tetsuo、Mori Seiichi
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Journal Title
Gynecologic Oncology
Volume: 160
Issue: 2
Pages: 547-556
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Potential Mechanism of Anticancer Immune Response Coincident With Immune-related Adverse Events in Patients With Renal Cell Carcinoma2020
Author(s)
Kato T, Tomiyama E, Koh Y, Matsushita M, Hayashi Y, Nakano K, Ishizuya YU, Wang C, Hatano K, Kawashima A, Ujike T, Kawasaki K, Morii E, Gotoh K, Eguchi H, Kiyotani K, Fujita K, Nonomura N, Uemura M.
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Journal Title
Anticancer Research
Volume: 40
Issue: 9
Pages: 4875-4883
DOI
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Peer Reviewed / Open Access
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[Journal Article] Diagnostic utility of STAT6YE361 expression in classical Hodgkin lymphoma and related entities2019
Author(s)
Slambrouck CV, Huh J, Suh C, Song JY, Menon MP, Sohani AR, Duffield AS, Goldberg RC, Dama P, Kiyotani K, Godfrey J, Fitzpatrick C, Kline J, Smith SM, Jaffe ES, Hartmann S, Venkataraman G.
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Journal Title
Modern Pathology
Volume: 33
Issue: 5
Pages: 834-845
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Secreted PD-L1 variants mediate resistance to PD-L1 blockade therapy in non-small cell lung cancer2019
Author(s)
Gong Bo, Kiyotani Kazuma, Sakata Seiji, Nagano Seiji, Kumehara Shun, Baba Satoko, Besse Benjamin, Yanagitani Noriko, Friboulet Luc, Nishio Makoto, Takeuchi Kengo, Kawamoto Hiroshi, Fujita Naoya, Katayama Ryohei
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Journal Title
The Journal of Experimental Medicine
Volume: 216
Issue: 4
Pages: 982-1000
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A Peptoid with Ectended Shape in Water2019
Author(s)
Morimoto J, Fukuda Y, Kuroda D, Watanabe T, Yoshida F, Asada M, Nakamura T, Senoo A, Nagatoishi S, Tsumoto K, *Sando S
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Journal Title
J Am Chem Soc.
Volume: 141
Issue: 37
Pages: 14612-14623
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Peer Reviewed
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[Presentation] Early dynamics of T cell clonotypes as potential surrogate biomarker for immune checkpoint inhibitors.2021
Author(s)
Kato T, Kiyotani K, Yamamoto A, Uemura T, Yamamichi G, Tomiyama E, Koh Y, Matsushita M, Hatano K, Kawashima A, Uemura M, Nonomura N.
Organizer
第80回日本癌学会
Related Report
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[Presentation] Generation of neoantigen-specific T cells for adoptive cell transfer for treating head and neck squamous cell carcinoma.2021
Author(s)
Lili R, Wei T, Leisegang M, Xia M, Kiyotani K, Li N, Zeng C, Deng C, Jiang J, Harada M, Agrawal N, Li L, Qi H, Nakamura Y.
Organizer
第80回日本癌学会
Related Report
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[Presentation] Epigenetic alteration of SALL3 contributes to chemoresistance in triple-negative breast cancer.2021
Author(s)
Matsushita Y, Komatsu M, Kiyotani K, Niinuma T, Suzuki H, Yoshimaru T, Tajima A, Imoto I, Honda J, Furukawa Y, Nakamura Y, Miyoshi Y, Sasa M, Katagiri T.
Organizer
第80回日本癌学会
Related Report
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[Presentation] Combined targeting of tumor-stroma and cancer cells by T cells is essential for eradication of solid tumors2020
Author(s)
Steven P. Wolf, Vasiliki Anastasopoulou, Madeline Steiner, Markus I. Diehl, Kimberley Borutta, Boris Engels, Poh Yin Yew, Kazuma Kiyotani, Yusuke Nakamura, Karin Schreiber, Hans Schreiber, Matthias Leisegang
Organizer
第79回日本癌学会
Related Report
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[Presentation] Comparison of TCR repertoires between cancer tissues and lymph nodes in colorectal cancer patients.2019
Author(s)
Kiyotani K, Matsuda T, Miyauchi E, Hsu Y, Nagayama S, Zewde M, Park JH, Kato T, Harada M, Suzuki N, Nagano H, Hazama S, Nakamura Y.
Organizer
AACR Annual Meeting 2019
Related Report
Int'l Joint Research
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