| Item type |
文献 / Documents(1) |
| 公開日 |
2019-03-05 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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|
関連識別子 |
https://doi.org/10.18632/oncotarget.25132 |
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関連名称 |
10.18632/oncotarget.25132 |
| 出版タイプ |
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出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Anti-podocalyxin antibody exerts antitumor effects via antibody-dependent cellular cytotoxicity in mouse xenograft models of oral squamous cell carcinoma |
| 著者 |
イタイ, シュンスケ
オオイシ, トモカズ
カネコ, ミカ
ヤマダ, シンジ
阿部, 真治
ナカムラ, タクロウ
ヤナカ, ミユキ
Chang, Yao-Wen
オオバ, シュンイチ
西岡, 安彦
カワダ, マナブ
ハラダ, ヒロユキ
カトウ, ユキナリ
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| 抄録 |
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内容記述 |
Podocalyxin (PODXL) overexpression is associated with progression, metastasis, and poor outcomes in cancers. We recently produced the novel anti-PODXL monoclonal antibody (mAb) PcMab-47 (IgG1, kappa). Herein, we engineered PcMab-47 into 47-mG2a, a mouse IgG2a-type mAb, to add antibody-dependent cellular cytotoxicity (ADCC). We further developed 47-mG2a-f, a core fucose-deficient type of 47-mG2a to augment its ADCC. Immunohistochemical analysis of oral cancer tissues using PcMab-47 and 47-mG2a revealed that the latter stained oral squamous cell carcinoma (OSCC) cells in a cytoplasmic pattern at a much lower concentration. PcMab-47 and 47-mG2a detected PODXL in 163/201 (81.1%) and in 197/201 (98.0%) OSCC samples, respectively. 47-mG2a-f also detected PODXL in OSCCs at a similar frequency as 47-mG2a. In vitro analysis revealed that both 47-mG2a and 47-mG2a-f exhibited strong complement-dependent cytotoxicity (CDC) against CHO/hPODXL cells. In contrast, 47-mG2a-f exhibited much stronger ADCC than 47-mG2a against OSCC cells, indicating that ADCC and CDC of those anti-PODXL mAbs depend on target cells. In vivo analysis revealed that both 47-mG2a and 47-mG2a-f exerted antitumor activity in CHO/hPODXL xenograft models at a dose of 100 μg or 500 μg/mouse/week administered twice. 47-mG2a-f, but not 47-mG2a, exerted antitumor activity in SAS and HSC-2 xenograft models at a dose of 100 μg/mouse/week administered three times. Although both 47-mG2a and 47-mG2a-f exerted antitumor activity in HSC-2 xenograft models at a dose of 500 μg/mouse/week administered twice, 47-mG2a-f also showed higher antitumor activity than 47-mG2a. These results suggested that a core fucose-deficient anti-PODXL mAb could be useful for antibody-based therapy against PODXL-expressing OSCCs. |
| キーワード |
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|
主題 |
podocalyxin |
| キーワード |
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主題 |
PODXL |
| キーワード |
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|
主題 |
monoclonal antibody |
| キーワード |
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|
主題 |
antibody-dependent cellular cytotoxicity |
| キーワード |
|
|
主題 |
oral squamous cell carcinoma |
| 書誌情報 |
en : Oncotarget
巻 9,
号 32,
p. 22480-22497,
発行日 2018-04-27
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
19492553 |
| 出版者 |
|
|
出版者 |
Impact Journals, LLC |
| 権利情報 |
|
|
権利情報 |
Copyright: Itai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
|
|
識別子 |
347641 |
| 言語 |
|
|
言語 |
eng |
onc_9_32_22480.pdf (4.91 MB)
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