| 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 |
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| Research Field |
Tumor therapeutics
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| Research Institution | The University of Tokyo |
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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 |
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| 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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