Antipodoplanin antibody enhances the antitumor effects of CTLA-4 blockade against malignant mesothelioma by natural killer cells

• 資料種別: 博士論文
• タイトル: Antipodoplanin antibody enhances the antitumor effects of CTLA-4 blockade against malignant mesothelioma by natural killer cells
• 著者・編者: Yoneda, Hiroto; Mitsuhashi, Atsushi; Yoshida, Aito; Ogino, Hirokazu; Itakura, Satoshi; Nguyen, Na Thi; Nokihara, Hiroshi; Sato, Seidai; Shinohara, Tsutomu; Hanibuchi, Masaki; Abe, Shinji; Kaneko, Mika K.; Kato, Yukinari; Nishioka, Yasuhiko
• 著者標目: Yoneda, Hiroto; Mitsuhashi, Atsushi; Yoshida, Aito; Ogino, Hirokazu; Itakura, Satoshi; Nguyen, Na Thi; Nokihara, Hiroshi; Sato, Seidai; Shinohara, Tsutomu; Hanibuchi, Masaki; Abe, Shinji; Kaneko, Mika K.; Kato, Yukinari; Nishioka, Yasuhiko
• 出版事項: Japanese Cancer Association|John Wiley & Sons
• 出版年月日等: 2023-12-26
• 出版年（W3CDTF）: 2023-12-26
• 並列タイトル等: 抗ポドプラニン抗体はナチュラルキラー細胞による悪性中皮腫に対する抗CTLA-4抗体の抗腫瘍効果を増強する
• タイトル（掲載誌）: Cancer Science
• 巻号年月日等（掲載誌）: 115 2
• 掲載巻: 115
• 掲載号: 2
• 掲載ページ: 357-368
• ISSN（掲載誌）: ISSN : 1347-9032; ISSN : 1349-7006
• 授与機関名: 徳島大学
• 授与年月日: 2024-06-27
• 報告番号: 甲第3835号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: CTLA-14; NK cell; Immune checkpoint inhibitor; Malignant pleural mesothelioma; Podoplanin
• 対象利用者: 一般
• 一般注記: 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.
• オンライン閲覧公開範囲: インターネット公開
• 著作権情報: 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.
• 関連情報（DOI）: 10.1111/cas.16046
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

http://repo.lib.tokushima-u.ac.jp/files/public/11/119228/2024071009302571668/k3835_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/119228/20240710093025189625/k3835_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/119228/20240710093025493832/k3835_fulltext.pdf fulltext