ID | 119228 |
著者 |
米田, 浩人
Tokushima University
Yoshida, Aito
Tokushima University
荻野, 広和
Tokushima University
Itakura, Satoshi
Tokushima University
Nguyen, Na Thi
Tokushima University
軒原, 浩
Tokushima University
Kaneko, Mika K.
Tohoku University
Kato, Yukinari
Tohoku University
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キーワード | CTLA-14
immune checkpoint inhibitor
malignant pleural mesothelioma
NK cell
podoplanin
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資料タイプ |
学術雑誌論文
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抄録 | Combination immunotherapy with multiple immune checkpoint inhibitors (ICIs) has been approved for various types of malignancies, including malignant pleural mesothelioma (MPM). Podoplanin (PDPN), a transmembrane sialomucin-like glycoprotein, has been investigated as a diagnostic marker and therapeutic target for MPM. We previously generated and developed a PDPN-targeting Ab reagent with high Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the effects of anti-PDPN Abs on various tumor-infiltrating immune cells and their synergistic effects with ICIs have remained unclear. In the present study, we established a novel rat–mouse chimeric anti- mouse PDPN IgG2a mAb (PMab-1-mG2a) and its core-fucose-deficient Ab (PMab-1-mG2a-f) to address these limitations. We identified the ADCC and CDC activity of PMab-1-mG2a-f against the PDPN-expressing mesothelioma cell line AB1-HA. The antitumor effect of monotherapy with PMab-1-mG2a-f was not sufficient to overcome tumor progression in AB1-HA-bearing immunocompetent mice. However, PMab-1-mG2a-f enhanced the antitumor effects of CTLA-4 blockade. Combination therapy with anti-PDPN Ab and anti-CTLA-4 Ab increased tumor-infiltrating natural killer (NK) cells. The depletion of NK cells inhibited the synergistic effects of PMab-1-mG2a-f and CTLA-4 blockade in vivo. These findings indicated the essential role of NK cells in novel combination immunotherapy targeting PDPN and shed light on the therapeutic strategy in advanced MPM.
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掲載誌名 |
Cancer Science
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ISSN | 13479032
13497006
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出版者 | Japanese Cancer Association|John Wiley & Sons
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巻 | 115
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号 | 2
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開始ページ | 357
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終了ページ | 368
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発行日 | 2023-12-26
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権利情報 | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
出版社版
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部局 |
病院
医学系
薬学系
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