『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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種別 (必須): 学術論文 (審査論文) [継承]
言語 (必須): 英語 [継承]
招待 (推奨):
審査 (推奨):
カテゴリ (推奨):
共著種別 (推奨):
学究種別 (推奨):
組織 (推奨):
著者 (必須): 1. (英) Asano Ryutaro (日) (読)
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貢献度 (任意):
学籍番号 (推奨):
[継承]
2. (英) Shimomura Ippei (日) (読)
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学籍番号 (推奨):
[継承]
3. (英) Konno Shota (日) (読)
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学籍番号 (推奨):
[継承]
4. (英) Ito Akiko (日) (読)
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学籍番号 (推奨):
[継承]
5. (英) Masakari Yosuke (日) (読)
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学籍番号 (推奨):
[継承]
6. (英) Orimo Ryota (日) (読)
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[継承]
7. (英) Taki Shintaro (日) (読)
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[継承]
8. (英) Arai Kyoko (日) (読)
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[継承]
9. (英) Ogata Hiromi (日) (読)
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[継承]
10. (英) Okada Mai (日) (読)
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[継承]
11. (英) Furumoto Shozo (日) (読)
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[継承]
12.鬼塚 正義 ([徳島大学.大学院社会産業理工学研究部.生物資源産業学域.応用生命系.生体分子機能学分野]/[徳島大学.生物資源産業学部.生物資源産業学科.応用生命講座])
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貢献度 (任意):
学籍番号 (推奨):
[継承]
13.大政 健史
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[継承]
14. (英) Hayashi Hiroki (日) (読)
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[継承]
15. (英) Katayose Yu (日) (読)
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[継承]
16. (英) Unno Michiaki (日) (読)
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[継承]
17. (英) Kudo Toshio (日) (読)
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[継承]
18. (英) Umetsu Mitsuo (日) (読)
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学籍番号 (推奨):
[継承]
19. (英) Kumagai Izumi (日) (読)
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学籍番号 (推奨):
[継承]
題名 (必須): (英) Rearranging the domain order of a diabody-based IgG-like bispecific antibody enhances its antitumor activity and improves its degradation resistance and pharmacokinetics.  (日)    [継承]
副題 (任意):
要約 (任意): (英) One approach to creating more beneficial therapeutic antibodies is to develop bispecific antibodies (bsAbs), particularly IgG-like formats with tetravalency, which may provide several advantages such as multivalent binding to each target antigen. Although the effects of configuration and antibody-fragment type on the function of IgG-like bsAbs have been studied, there have been only a few detailed studies of the influence of the variable fragment domain order. Here, we prepared four types of hEx3-scDb-Fc, IgG-like bsAbs, built from a single-chain hEx3-Db (humanized bispecific diabody [bsDb] that targets epidermal growth factor receptor and CD3), to investigate the influence of domain order and fusion manner on the function of a bsDb with an Fc fusion format. Higher cytotoxicities were observed with hEx3-scDb-Fcs with a variable light domain (VL)-variable heavy domain (VH) order (hEx3-scDb-Fc-LHs) compared with a VH-VL order, indicating that differences in the Fc fusion manner do not affect bsDb activity. In addition, flow cytometry suggested that the higher cytotoxicities of hEx3-scDb-Fc-LH may be attributable to structural superiority in cross-linking. Interestingly, enhanced degradation resistance and prolonged in vivo half-life were also observed with hEx3-scDb-Fc-LH. hEx3-scDb-Fc-LH and its IgG2 variant exhibited intense in vivo antitumor effects, suggesting that Fc-mediated effector functions are dispensable for effective anti-tumor activities, which may cause fewer side effects. Our results show that merely rearranging the domain order of IgG-like bsAbs can enhance not only their antitumor activity, but also their degradation resistance and in vivo half-life, and that hEx3-scDb-Fc-LHs are potent candidates for next-generation therapeutic antibodies.  (日)    [継承]
キーワード (推奨): 1. (英) Animals (日) (読) [継承]
2. (英) Antibodies, Bispecific (日) (読) [継承]
3. (英) Antigens, CD3 (日) (読) [継承]
4. (英) Antineoplastic Agents (日) (読) [継承]
5. (英) Area Under Curve (日) (読) [継承]
6. (英) Binding Sites (日) (読) [継承]
7. (英) Cell Line, Tumor (日) (読) [継承]
8. (英) Cell Proliferation (日) (読) [継承]
9. (英) Cell Survival (日) (読) [継承]
10. (英) Dose-Response Relationship, Drug (日) (読) [継承]
11. (英) Female (日) (読) [継承]
12. (英) Humans (日) (読) [継承]
13. (英) Immunoglobulin G (日) (読) [継承]
14. (英) Interferon-gamma (日) (読) [継承]
15. (英) MCF-7 Cells (日) (読) [継承]
16. (英) Mice, SCID (日) (読) [継承]
17. (英) Neoplasms (日) (読) [継承]
18. (英) Protein Binding (日) (読) [継承]
19. (英) Receptor, Epidermal Growth Factor (日) (読) [継承]
20. (英) Tumor Burden (日) (読) [継承]
21. (英) Xenograft Model Antitumor Assays (日) (読) [継承]
発行所 (推奨):
誌名 (必須): mAbs ([Taylor & Francis])
(pISSN: 1942-0862, eISSN: 1942-0870)

ISSN (任意): 1942-0870
ISSN: 1942-0862 (pISSN: 1942-0862, eISSN: 1942-0870)
Title: mAbs
Title(ISO): MAbs
Publisher: Taylor & Francis
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
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(必須): 6 [継承]
(必須): 5 [継承]
(必須): 1243 1254 [継承]
都市 (任意):
年月日 (必須): 西暦 2014年 10月 30日 (平成 26年 10月 30日) [継承]
URL (任意):
DOI (任意): 10.4161/mabs.29445    (→Scopusで検索) [継承]
PMID (任意): 25517309    (→Scopusで検索) [継承]
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備考 (任意): 1.(英) PublicationType: Journal Article  (日)    [継承]
2.(英) PublicationType: Research Support, Non-U.S. Gov't  (日)    [継承]

標準的な表示

和文冊子 ● Ryutaro Asano, Ippei Shimomura, Shota Konno, Akiko Ito, Yosuke Masakari, Ryota Orimo, Shintaro Taki, Kyoko Arai, Hiromi Ogata, Mai Okada, Shozo Furumoto, Masayoshi Onitsuka, Takeshi Omasa, Hiroki Hayashi, Yu Katayose, Michiaki Unno, Toshio Kudo, Mitsuo Umetsu and Izumi Kumagai : Rearranging the domain order of a diabody-based IgG-like bispecific antibody enhances its antitumor activity and improves its degradation resistance and pharmacokinetics., mAbs, Vol.6, No.5, 1243-1254, 2014.
欧文冊子 ● Ryutaro Asano, Ippei Shimomura, Shota Konno, Akiko Ito, Yosuke Masakari, Ryota Orimo, Shintaro Taki, Kyoko Arai, Hiromi Ogata, Mai Okada, Shozo Furumoto, Masayoshi Onitsuka, Takeshi Omasa, Hiroki Hayashi, Yu Katayose, Michiaki Unno, Toshio Kudo, Mitsuo Umetsu and Izumi Kumagai : Rearranging the domain order of a diabody-based IgG-like bispecific antibody enhances its antitumor activity and improves its degradation resistance and pharmacokinetics., mAbs, Vol.6, No.5, 1243-1254, 2014.

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