Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo.

• Material Type: 博士論文
• Title: Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo.
• Author/Editor: Yasuda, Satoshi; Sho, Masayuki; Yamato, Ichiro; Yoshiji, Hitoshi; Wakatsuki, Kohei; Nishiwada, Satoshi; Yagita, Hideo; Nakajima, Yoshiyuki
• Author Heading: Yasuda, Satoshi; Sho, Masayuki; Yamato, Ichiro; Yoshiji, Hitoshi; Wakatsuki, Kohei; Nishiwada, Satoshi; Yagita, Hideo; Nakajima, Yoshiyuki
• Publication, Distribution, etc.: Oxford University Press
• Publication Date: 2013-06
• Publication Date (W3CDTF): 2013-06
• Alternative Title: PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果
• Periodical title: Clinical and experimental immunology
• No. or year of volume/issue: 172 3
• Volume: 172
• Issue: 3
• Pages: 500-506
• ISSN (Periodical Title): ISSN : 0009-9104
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2013-05-29
• Dissertation Number: 甲第600号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: PD-1; VEGFR2; Immune checkpoint; Antiangiogenesis; Antitumour immunity
• Target Audience: 一般
• Note (General): type:Thesis; Recent basic and clinical studies have shown that the programmed death ligand (PD-L)/PD-1 pathway has a significant role in tumour immunity, and its blockade has a therapeutic potential against several human cancers. We hypothesized that anti-angiogeneic treatment might augment the efficacy of PD-1 blockade. To this end, we evaluated combining the blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2) in a murine cancer model using Colon-26 adenocarcinoma. Interestingly, simultaneous treatment with anti-PD-1 and anti-VEGFR2 monoclonal antibodies (mAbs) inhibited tumour growth synergistically in vivo without overt toxicity. Blocking VEGFR2 inhibited tumour neovascularization significantly, as demonstrated by the reduced number of microvessels, while PD-1 blockade had no impact on tumour angiogenesis. PD-1 blockade might promote T cell infiltration into tumours and significantly enhanced local immune activation, as shown by the up-regulation of several proinflammatory cytokine expressions. Importantly, VEGFR2 blockade did not interfere with T cell infiltration and immunological activation induced by PD-1 blockade. In conclusion, simultaneous blockade of PD-1 and VEGFR2 induced a synergistic in-vivo anti-tumour effect, possibly through different mechanisms that might not be mutually exclusive. This unique therapeutic strategy may hold significant promise for future clinical application.; 博士（医学）・甲第600号・平成25年5月29日; © 2013 British Society for Immunology; This article has been accepted for publication in Clinical and experimental immunology Published by Oxford University Press.; identifier:Clinical and experimental immunology Vol.172 No.3 p.500-506 (2013 Jun); identifier:00099104; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2588; identifier:Clinical and experimental immunology, 172(3): 500-506
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1111/cei.12069
• Data Provider (Database): 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
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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