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滑膜肉腫に対するHER2を標的としたCAR-T細胞療法
http://hdl.handle.net/10191/0002000861
http://hdl.handle.net/10191/0002000861d8dbd844-dd4f-4a22-97ef-1063121b5915
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本文 (4.34MB)
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要旨 (561KB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2023-03-07 | |||||||||
| タイトル | ||||||||||
| タイトル | Effectiveness of 4-1BB-costimulated HER2-targeted chimeric antigen receptor T cell therapy for synovial sarcoma | |||||||||
| 言語 | en | |||||||||
| タイトル | ||||||||||
| タイトル | 滑膜肉腫に対するHER2を標的としたCAR-T細胞療法 | |||||||||
| 言語 | ja | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Synovial sarcoma | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | HER2 | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Chimeric antigen receptor | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | T cell | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Cancer immunotherapy | |||||||||
| 資源タイプ | ||||||||||
| 資源 | http://purl.org/coar/resource_type/c_db06 | |||||||||
| タイプ | doctoral thesis | |||||||||
| アクセス権 | ||||||||||
| アクセス権 | open access | |||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
| 著者 |
村山, 雄大
× 村山, 雄大
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| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Background: Synovial sarcoma is a rare malignant soft-tissue tumor that is prevalent in adolescents and young adults, and poor prognosis has been reported in patients with metastatic lesions. Chimeric antigen receptor (CAR) T-cell therapy is an emerging novel therapy for solid tumors; however, its application in synovial sarcoma has not yet been explored. Methods: A novel human epidermal growth factor receptor 2 (HER2)-targeted CAR containing scFv-FRP5, CD8α hinge and transmembrane domains as well as 4-1BB costimulatory and CD3ζ signaling domains was developed. Three synovial sarcoma cell lines that expressed the fusion transcript SS18-SSX1/2/4 were used in the study. Cytokine secretion assay, cytotoxicity assay, and real-time cell analysis experiments were conducted to confirm the function of T cells transduced with the CAR gene. Results: High cell-surface expression of HER2 was observed in all the cell lines. HER2-targeted/4-1BB-costimulated CAR T cells specifically recognized the synovial sarcoma cells, secreted interferon gamma and tumor necrosis factor alpha, and exerted cytotoxic effects in these cells. Conclusion: To the best of our knowledge, this is the first study to indicate that HER2-targeted CAR T cells are directly effective against molecularly defined synovial sarcoma cells. Furthermore, our findings might set the basis for developing improved CAR T cell-based therapies for chemo-refractory or relapsed synovial sarcoma. | |||||||||
| 言語 | en | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | Translational oncology. 2021, 14(12), 101227. | |||||||||
| 言語 | en | |||||||||
| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | https://doi.org/10.1016/j.tranon.2021.101227 | |||||||||
| 権利 | ||||||||||
| 言語 | en | |||||||||
| 権利情報 | © 2021 The Authors. Published by Elsevier Inc. | |||||||||
| 権利 | ||||||||||
| 言語 | en | |||||||||
| 権利情報Resource | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||||
| 権利情報 | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士（医学） | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||
| 学位授与機関識別子 | 13101 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 新潟大学 | |||||||||
| 言語 | en | |||||||||
| 学位授与機関名 | Niigata University | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2022-03-23 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第5005号 | |||||||||
| 学位記番号 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 新大院博(医)第1075号 | |||||||||
| 言語 | ja | |||||||||
