Reference - Detail
| RRC ID | 44395 |
|---|---|
| Author | Yasuda S, Sho M, Yamato I, Yoshiji H, Wakatsuki K, Nishiwada S, Yagita H, Nakajima Y. |
| Title | Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo. |
| Journal | Clin Exp Immunol |
| 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. |
| Volume | 172(3) |
| Pages | 500-6 |
| Published | 2013-6-1 |
| DOI | 10.1111/cei.12069 |
| PMID | 23600839 |
| PMC | PMC3646450 |
| MeSH | Adenocarcinoma / blood supply Adenocarcinoma / immunology Adenocarcinoma / therapy Angiogenesis Inhibitors / administration & dosage Animals Antibodies, Monoclonal / administration & dosage Cell Line, Tumor Colonic Neoplasms / blood supply Colonic Neoplasms / immunology Colonic Neoplasms / therapy Drug Synergism Female Humans Lymphocytes, Tumor-Infiltrating / immunology Mice Mice, Inbred BALB C Neoplasms, Experimental / blood supply Neoplasms, Experimental / immunology Neoplasms, Experimental / therapy* Neovascularization, Pathologic / prevention & control Programmed Cell Death 1 Receptor / antagonists & inhibitors* Programmed Cell Death 1 Receptor / immunology Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors* Vascular Endothelial Growth Factor Receptor-2 / immunology |
| IF | 3.532 |
| Times Cited | 89 |
| WOS Category | IMMUNOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 57 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| Human and Animal Cells | Colon-26(RCB2657) |