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Systemic CD8+ T Cell-mediated Tumoricidal Effects by Intratumoral Treatment of Oncolytic Herpes Simplex Virus with the Agonistic Monoclonal Antibody for Murine Glucocorticoid-induced Tumor Necrosis Factor Receptor
http://hdl.handle.net/10076/14717
http://hdl.handle.net/10076/147171115cc53-3478-41b4-b18c-05b0744d7baf
名前 / ファイル | ライセンス | アクション |
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2014DM008.pdf (6.5 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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公開日 | 2015-10-09 | |||||||||||
タイトル | ||||||||||||
タイトル | Systemic CD8+ T Cell-mediated Tumoricidal Effects by Intratumoral Treatment of Oncolytic Herpes Simplex Virus with the Agonistic Monoclonal Antibody for Murine Glucocorticoid-induced Tumor Necrosis Factor Receptor | |||||||||||
言語 | en | |||||||||||
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言語 | eng | |||||||||||
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資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
資源タイプ | doctoral thesis | |||||||||||
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アクセス権 | open access | |||||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
著者 |
石原, 幹也
× 石原, 幹也
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抄録 | ||||||||||||
内容記述タイプ | Abstract | |||||||||||
内容記述 | Oncolytic virotherapy combined with immunomodulators is a novel noninvasive strategy for cancer treatment. In this study, we examined the tumoricidal effects of oncolytic HF10, a naturally occurring mutant of herpes simplex virus type-1, combined with an agonistic DTA-1 monoclonal antibody specific for the glucocorticoid-induced tumor necrosis factor receptor. Two murine tumor models were used to evaluate the therapeutic efficacies of HF10 virotherapy combined with DTA-1. The kinetics and immunological mechanisms of DTA-1 in HF10 infection were examined using flow cytometry and immunohistochemistry. Intratumoral administration of HF10 in combination with DTA-1 at a low dose resulted in a more vigorous attenuation of growth of the untreated contralateral as well as the treated tumors than treatment with either HF10 or DTA-1 alone. An accumulation of CD8(+) T cells, including tumor- and herpes simplex virus type-1-specific populations, and a decrease in the number of CD4(+) Foxp3(+) T regulatory cells were seen in both HF10- and DTA-1-treated tumors. Studies using Fc-digested DTA-1 and Fc gamma receptor knockout mice demonstrated the direct participation of DTA-1 in regulatory T cell depletion by antibody-dependent cellular cytotoxicity primarily via macrophages. These results indicated the potential therapeutic efficacy of a glucocorticoid-induced tumor necrosis factor receptor-specific monoclonal antibody in oncolytic virotherapy at local tumor sites. | |||||||||||
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内容記述タイプ | Other | |||||||||||
内容記述 | 本文 / Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Mie, Japan | |||||||||||
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内容記述タイプ | Other | |||||||||||
内容記述 | 18p | |||||||||||
書誌情報 |
発行日 2014-01-01 |
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DOI | ||||||||||||
識別子タイプ | DOI | |||||||||||
関連識別子 | 10.1371/journal.pone.0104669 | |||||||||||
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内容記述タイプ | Other | |||||||||||
内容記述 | application/pdf | |||||||||||
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出版タイプ | VoR | |||||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
出版者 | ||||||||||||
出版者 | 三重大学 | |||||||||||
出版者(ヨミ) | ||||||||||||
値 | ミエダイガク | |||||||||||
関係URI | ||||||||||||
関連名称 | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104669 | |||||||||||
学位名 | ||||||||||||
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 | 14101 | |||||||||||
学位授与機関名 | 三重大学 | |||||||||||
学位授与年月日 | ||||||||||||
学位授与年月日 | 2014-12-17 | |||||||||||
学位授与番号 | ||||||||||||
学位授与番号 | 甲医学第1693号 | |||||||||||
ノート | ||||||||||||
値 | PLOS ONE, 9 (8), 2014, ISSN: 1932-6203に掲載 | |||||||||||
資源タイプ(三重大) | ||||||||||||
値 | Doctoral Dissertation / 博士論文 |