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

• Material Type: 博士論文
• Title: Antipodoplanin antibody enhances the antitumor effects of CTLA-4 blockade against malignant mesothelioma by natural killer cells
• Author/Editor: 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
• Author Heading: 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
• Publication, Distribution, etc.: Japanese Cancer Association|John Wiley & Sons
• Publication Date: 2023-12-26; 115 2
• Publication Date (W3CDTF): 2023-12-26
• Alternative Title: 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
• Degree grantor/type: 徳島大学
• Date Granted: 2024-06-27
• Date Granted (W3CDTF): 2024-06-27
• Dissertation Number: 甲第3835号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: CTLA-14; NK cell; Immune checkpoint inhibitor; Malignant pleural mesothelioma; Podoplanin
• Target Audience: 一般
• Note (General): 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.
• Persistent ID (NDL): info:ndljp/pid/13730912; https://dl.ndl.go.jp/pid/13730912
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• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
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• Date Accepted (W3CDTF): 2024-08-02T22:09:17+09:00
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/119228
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