| Project/Area Number |
18K07285
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
OHTA RIEKO 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (30452460)
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| Co-Investigator(Kenkyū-buntansha) |
葛島 清隆 愛知県がんセンター(研究所), 腫瘍免疫応答研究分野, 分野長 (30311442)
今井 優樹 名古屋市立大学, 医薬学総合研究院(医学), 講師 (30440936)
岡村 文子 (出町文子) 愛知県がんセンター(研究所), 腫瘍免疫制御TR分野, 主任研究員 (10546948)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Ｔ細胞受容体 / 親和性の成熟 / がん特異的TCR / 膜侵襲複合体 / 補体 / T細胞受容体 / TCR |
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| Outline of Final Research Achievements |
In cancer patients, despite the expression of cancer-specific antigens in cancer tissue, serum antibody titers against cancer are low and the frequency of cancer-specific cytotoxic T cells (CTL, killer T cells) is low. In this study, we demonstrated the potential for in vitro affinity maturation of HLA-A24-restricted, which are present in approximately 60% of the Japanese population, cancer antigen-specific CTL clones using the 'method of TCR display system using 293T cells '. We were also able to construct a single chain variable fragment (scFv) that induces the formation of membrane attack complexes. Linking this scFv with high-affinity TCR mutants could lead to the development of new therapeutic reagents.
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| Academic Significance and Societal Importance of the Research Achievements |
日本人の大多数が有するHLA拘束性のがん抗原を認識するCTLクローンのTCRから、抗原に高親和性のTCRが取得できれば、日本人に適した新たながんのターゲティングが可能になると考えられる。今回、「293T細胞ディスプレイ法」を用いて、一価での親和性が低いTCRについて、高親和性TCRの取得に成功した。今後、この技術が応用され、種々のがん抗原に対する高親和性TCR を用いた薬剤の創製に寄与すると考えられる
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