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Immunotherapy using monoclonal antibodies targeting programmed death ligand-1 (PD-L1) on cancer cells as a biomarker of escape from response to immune checkpoint has demonstrated efficacy in treating many solid tumors. In addition, some of the signals, such as vascular endothelial growth factor (VEGF), bind to receptors on the surface of normal endothelial cells and encourage angiogenesis, or the formation and survival of new blood vessels. Due to the special features of nanobodies with high specificity and affinity as a powerful new tool in cancer therapy, here, a recombinant bispecific bivalent anti-PD-L1/VEGF nanobody was constructed and its functionality in inhibition of angiogenesis  in vitro  was investigated. Results demonstrated that bivalent anti-PD-L1/VEGF nanobody efficiently inhibited HUVEC and A431 cells proliferation and tube formation. In addition, bivalent anti-PD-L1/VEGF nanobody efficiently inhibited angiogenesis in an  ex ovo  Chick Chorioallantoic Membrane assay. The results indicate for the potential of bivalent anti-PD-L1/VEGF nanobody as a novel promising tool for cancer therapy.

Investigation of the therapeutic potential of recombinant bispecific bivalent anti-PD-L1/VEGF nanobody in inhibition of angiogenesis