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Oncolytic HSV-1 in combination with lenalidomide for plasma cell neoplasms
https://kagawa-u.repo.nii.ac.jp/records/7183
https://kagawa-u.repo.nii.ac.jp/records/71837fea194b-4f42-4891-ad3c-ae35eeeffc63
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本文 (791.5 kB)
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内容の要旨 (83.9 kB)
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審査の結果の要旨 (57.4 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-02-03 | |||||
| タイトル | ||||||
| タイトル | Oncolytic HSV-1 in combination with lenalidomide for plasma cell neoplasms | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| その他（別言語等）のタイトル | ||||||
| その他のタイトル | 形質細胞腫瘍に対するがん治療用HSV-1とレナリドミドの併用療法 | |||||
| 言語 | ja | |||||
| 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 |
奥, 真紀
× 奥, 真紀 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Oncolytic viruses exert an anti-tumour effect through two mechanisms: direct oncolytic and indirect immune-mediated mechanisms. Although oncolytic herpes simplex virus type 1 (HSV-1) has been approved for melanoma treatment and is being examined for its applicability to a broad spectrum of malignancies, it is not known whether it has an anti-myeloma effect. In the present study, we show that the third-generation oncolytic HSV-1, T-01, had a direct oncolytic effect on five of six human myeloma cell lines in vitro. The anti-tumour effect was enhanced in the presence of peripheral blood mononuclear cells (PBMCs) from healthy individuals and, to a lesser extent, from patients with myeloma. The enhancing effect of PBMCs was abrogated by blocking type I interferons (IFNs) or by depleting plasmacytoid dendritic cells (pDCs) or natural killer (NK) cells, suggesting that pDC-derived type I IFNs and NK cells dominated the anti-tumour effect. Furthermore, the combination of T-01 and lenalidomide exhibited enhanced cytotoxicity, and the triple combination of T-01, lenalidomide and IFN-α had a maximal effect. These data indicate that oncolytic HSV-1 represents a viable therapy for plasma cell neoplasms through direct oncolysis and immune activation governed by pDCs and NK cells. Lenalidomide is likely to augment the anti-myeloma effect of HSV-1. | |||||
| 言語 | en | |||||
| 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 | 16201 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 香川大学 | |||||
| 言語 | en | |||||
| 学位授与機関名 | Kagawa University | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-12-24 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第758号 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | Copyright © 2020 British Society for Haematology and John Wiley & Sons Ltd. | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | Embergo expiration date: 2021-11-20 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | This is the Accepted Version of the following article: Oncolytic herpes simplex virus type 1 (HSV‐1) in combination with lenalidomide for plasma cell neoplasms; British journal of haematology; Volume 192 Number 2 (2020）) Pages: 343-353; doi: 10.1111/bjh.17173, which has been published in final form at https://doi.org/10.1111/bjh.17173. | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 33216988 | |||||
| 関連サイト | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1111/bjh.17173 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | P | |||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | myeloma | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | oncolytic virus | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | HSV‐1 | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | lenalidomide | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | immunotherapy | |||||
| WAID | ||||||
| 値 | 3075 | |||||
| KEID | ||||||
| 値 | 29141 | |||||
