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ID 113062
著者
Itai, Shunsuke Tohoku University|Tokyo Medical and Dental University
Ohishi, Tomokazu Microbial Chemistry Research Foundation
Kaneko, Mika K. Tohoku University
Yamada, Shinji Tohoku University
Nakamura, Takuro Tohoku University
Yanaka, Miyuki Tohoku University
Chang, Yao-Wen Tohoku University
Ohba, Shun-Ichi Institute of Microbial Chemistry
Kawada, Manabu Microbial Chemistry Research Foundation
Harada, Hiroyuki Tokyo Medical and Dental University
Kato, Yukinari Tohoku University
キーワード
podocalyxin
PODXL
monoclonal antibody
antibody-dependent cellular cytotoxicity
oral squamous cell carcinoma
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Oncotarget
ISSN
19492553
出版者
Impact Journals, LLC
9
32
開始ページ
22480
終了ページ
22497
発行日
2018-04-27
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) (https://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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フルテキストファイル
言語
eng
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出版社版
部局
薬学系
医学系