Detection of neoantigens by gene-engineered T cells
Project/Area Number |
15K14403
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Tumor therapeutics
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Research Institution | The University of Tokyo |
Principal Investigator |
Kakimi Kazuhiro 東京大学, 医学部附属病院, 特任教授 (80273358)
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Co-Investigator(Kenkyū-buntansha) |
鈴木 隆二 独立行政法人国立病院機構(相模原病院臨床研究センター), 診断・治療研究室, 室長 (70373470)
松下 博和 東京大学, 医学部附属病院, 特任講師 (80597782)
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 腫瘍免疫 / ネオアンチゲン / TCR / レパトア解析 / 次世代シーケンサー / T細胞受容体 / がん抗原 |
Outline of Final Research Achievements |
Somatic mutations accumulate in cancer cells during cancer progression. Recent studies reported that T cells recognize antigens derived from tumor-specific mutated genes, so-called neoantigens, and mediate immune responses against tumor cells. These neoantigens are not expressed in the thymus and escape from the mechanism of central tolerance; thereby, their immunogenicity is higher than conventional tumor antigens. In this study, we developed the pipeline to predict and prioritize neoantigens by integrating RNA-Seq data with whole-exome sequencing. In addition, we demonstrated that T cell receptor gene sequencing technique using next-generation sequencer is quite useful to detect the expansion of antigen-reactive T cells. It is 1000-times more sensitive to detect antigen-reactive T cells than flowcytometry. Integrating these two novel techniques allow us to identify neoantigens and neoantigen-reactive T cells.
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Report
(3 results)
Research Products
(29 results)
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[Journal Article] Prediction and prioritization of neoantigens: integration of RNA sequencing data with whole-exome sequencing.2017
Author(s)
Karasaki T, Nagayama K, Kuwano H, Nitadori JI, Sato M, Anraku M, Hosoi A, Matsushita H, Takazawa M, Ohara O, Nakajima J, Kakimi K.
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Journal Title
Cancer Sci.
Volume: 108(2)
Issue: 2
Pages: 170-177
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Identification of Individual Cancer-Specific Somatic Mutations for Neoantigen-Based Immunotherapy of Lung Cancer.2016
Author(s)
Karasaki T, Nagayama K, Kawashima M, Hiyama N, Murayama T, Kuwano H, Nitadori J, Anraku M, Sato M, Miyai M, Hosoi A, Matsushita H, Kikugawa S, Matoba R, Ohara O, Kakimi K, Nakajima J
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Journal Title
Journal of Thoracic Oncology
Volume: 11(3)
Issue: 3
Pages: 324-33
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Detection and Tracking of NY-ESO-1-Specific CD8+ T Cells by High-Throughput T Cell Receptor β (TCRB) Gene Rearrangements Sequencing in a Peptide-Vaccinated Patient.2015
Author(s)
Miyai M, Eikawa S, Hosoi A, Iino T, Matsushita H, Isobe M, Uenaka A, Udono H, Nakajima J, Nakayama E, Kakimi K.
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Journal Title
PLoS One
Volume: 10(8)
Issue: 8
Pages: e0136086-e0136086
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients.2015
Author(s)
2.Kurose K, Ohue Y, Wada H, Iida S, Ishida T, Kojima T, Doi T, Suzuki S, Isobe M, Funakoshi T, Kakimi K, Nishikawa H, Udono H, Oka M, Ueda R, Nakayama E.
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Journal Title
Clin Cancer Res.
Volume: 21
Issue: 19
Pages: 4327-36
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Immunogram for Cancer-Immunity Cycle towards Personalized Immunotherapy of Lung Cancer2016
Author(s)
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
Organizer
IASLC 17th World Conference on Lung Cancer
Place of Presentation
Vienna, Austria
Related Report
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[Presentation] The detection and tracking of NY-ESO-1-specific CD8+ T cells by next generation sequencing of human TCRB CDR3 rearrangements.2015
Author(s)
Manami Miyai, Shingo Eikawa, Akihiro Hosoi, Tamaki Iino, Hirokazu Matsushita, Midori Isobe, Akiko Uenaka, Heiichiro Udono, Jun Nakajima, Eiichi Nakayama, Kazuhiro Kakimi
Organizer
第19回日本がん免疫学会総会(ICCIM2015)
Place of Presentation
伊藤国際学術研究センター(東京都文京区)
Year and Date
2015-07-09
Related Report
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