| Project/Area Number |
21K16659
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
MURATA Kenji 札幌医科大学, 医学部, 特任助教 (80722454)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 骨軟部肉腫 / 肉腫抗原 / 肉腫浸潤Tリンパ球 / T細胞受容体 / 腫瘍免疫 / 肉腫浸潤 Tリンパ球 / 単細胞解析 / TCR・抗原ペア / 養子免疫療法 |
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| Outline of Research at the Start |
骨軟部肉腫（以下、肉腫）に対する養子免疫療法の開発は、癌腫と比べて進展しておらず、抗原特異的なT細胞受容体（TCR）遺伝子を導入したT細胞輸注療法は一部の肉腫に対してしか適応していない。本研究では、肉腫浸潤Tリンパ球（TIL）のTCRレパトア解析を単細胞レベルで行い、そのTCRを抗原同定のプローベとして用いることで、肉腫反応性TCRと肉腫抗原を同時に同定することが可能なプラットフォームを確立し、肉腫に対する効果的な養子免疫療法の開発につなげる。
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| Outline of Final Research Achievements |
Tumor-infiltrating lymphocytes (TILs) were isolated from resected specimens of two cases of leiomyosarcoma, and TCR repertoire and gene expression analysis were performed at a single-cell level. In both cases, highly clonal T cells were identified and these T cells were likely to recognize the tumor. We selected multiple TCRs and generated TCR-transduced T cells (TCR-T cells) for each of them. Since autologous tumor cell lines could not be established, cDNA libraries were constructed from RNA extracted from the tumor cells. These cDNA libraries were then transfected into HEK293T cells overexpressing the patient’s HLA. Subsequently, we co-cultured TCR-T cells with these target cells to confirm immune responses and attempt to detect any positive reactions.
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| Academic Significance and Societal Importance of the Research Achievements |
骨軟部肉腫（以下、肉腫）に対する養子免疫療法の開発は、癌腫と比べて進展しておらず、抗原特異的なT細胞受容体（TCR）遺伝子を導入したT細胞輸注療法は一部の肉腫に対してしか適応していない。肉腫に対する効果的な遺伝子改変T細胞療法の実行化に向けて、肉腫浸潤Tリンパ球（TIL）由来の肉腫反応性TCRが認識する抗原を同定するための新たな解析プラットフォームを開発する。
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