An Antiangiogenic Agent Associated with Multi-Targets Exhibits Synergistic Antitumor Effects in Combination with Immunotherapeutics

Recently, an increasing number of studies have focused on the combination of antiangiogenic agents and Immune Checkpoint Inhibitors (ICIs) in preclinical and clinical settings. In this commentary, we discuss the combination of recombinant human endostatin (Endostar, Simcere) with immunotherapy. Similar to the anti-vascular endothelial growth factor (VEGF) antibody BD0801, Endostar is an antiangiogenic agent with VEGF binding affinity. In addition, Endostar binds to basic Fibroblast Growth Factor (bFGF) and blocks the binding of bFGF to FGF receptor 1 (FGFR1). Endostar in combination with anti-PD-L1 antibody showed synergistic antitumor effects in both colorectal cancer and melanoma mouse models. Furthermore, VEGF concentrations in the serum of tumor-bearing mice were significantly decreased upon Endostar and combination treatments. Significantly, increased CD8+ T cell infiltration and reduced Microvessel Density (MVD) in tumors were observed in the combination group. In conclusion, Endostar exerted a synergistic antitumor effect with immunotherapy, revealing a mechanism of synergy in the combination of antiangiogenic agents and immunotherapy involving tumor microenvironment modulation.