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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2588

Title: Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo
Other Titles: PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果
Authors: Yasuda, Satoshi
Sho, Masayuki
Yamato, Ichiro
Yoshiji, Hitoshi
Wakatsuki, Kohei
Nishiwada, Satoshi
Yagita, Hideo
Nakajima, Yoshiyuki
Keywords: PD-1
Immune checkpoint
Antitumour immunity
Issue Date: Jun-2013
Publisher: Blackwell Scientieic
Citation: Clinical and experimental immunology Vol.172 No.3 p.500-506
Abstract: 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.
Description: 博士(医学)・甲第600号・平成25年5月29日
URI: http://hdl.handle.net/10564/2588
ISSN: 00099104
Academic Degrees and number: 24601A600
Degree-granting date: 2013-05-29
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2013年度

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