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

Summary 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 ( VEGFR 2) in a murine cancer model using Colon‐26 adenocarcinoma. Interestingly, simultaneous treatment with anti‐ PD ‐1 and anti‐ VEGFR 2 monoclonal antibodies ( mAbs) inhibited tumour growth synergistically in vivo without overt toxicity. Blocking VEGFR 2 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, VEGFR 2 blockade did not interfere with T cell infiltration and immunological activation induced by PD ‐1 blockade. In conclusion, simultaneous blockade of PD ‐1 and VEGFR 2 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.