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

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;発行元の猶予期間終了の後、本文を登録予定(2014.06);開始ページ : 500;終了ページ : 506;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/23600839

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書名 Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo
著作者等 Nakajima, Yoshiyuki
Nishiwada, Satoshi
Sho, Masayuki
Wakatsuki, Kohei
Yagita, Hideo
Yamato, Ichiro
Yoshiji, Hitoshi
Yasuda, Satoshi
書名別名 PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果
出版元 Blackwell Scientieic
刊行年月 1966-
ISSN 00099104
NCID AA00607716
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言語 英語
出版国 イギリス
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