2019 Fiscal Year Final Research Report
Investigation of neo-self antigens derived from proteins with post-translational modification
| Project/Area Number |
18K19485
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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 50:Oncology and related fields
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| Research Institution | Japanese Foundation for Cancer Research |
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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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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Keywords | 翻訳後修飾 / ネオセルフ抗原 / T細胞受容体 / ネオアンチゲン |
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| Outline of Final Research Achievements |
In this study, we investigated whether neo-self peptides derived from mutilated proteins encoded by oncogenes. We generated all possible peptides with methylated amino acid using bioinformatic approach and predicted their binding affinities to HLA class I molecules. Through the analysis, we obtained two possible candidates of methylated proteins which can be presented on HLA molecules. From HLA-matched healthy donor’s blood sample, we successfully induced methylated peptide-specific T cells for one of them. We also identified the TCRalpha/beta sequences of the T cells, and generated TCR-engineered T cells.
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| Free Research Field |
腫瘍免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、翻訳後修飾（特にメチル化）を受けたタンパク質由来の抗原がT細胞の標的となりうるかを検証した。これまでに翻訳後修飾を受けたペプチドがHLA上に提示されていることは報告されていた。本研究では、実際に初めて翻訳後修飾を受けたペプチドを特異的に認識するT細胞の同定に成功した。本研究の成果は、学術的にも、また新たながん免疫療法の標的としても大変重要な成果である。
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