並列タイトル等PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果
タイトル（掲載誌）Clinical and experimental immunology
一般注記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
DOIinfo:doi/10.1111/cei.12069
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