Anti-tumor immunotherapy by blockade of the PD-1/PD-L1 pathway with recombinant human PD-1–IgV

BackgroundBlockade of the programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway can delay tumor growth and prolong the survival of tumor-bearing mice. The extracellular immunoglobulin (Ig) V domain of PD-1 is important for the interaction between PD-1 and PD-L1, suggesting that PD-1–IgV may be a potential target for anti-tumor immunotherapy.MethodsThe extracellular sequence of human PD-1–IgV (hPD-1–IgV) was expressed in Escherichia coli and purified. The anti-tumor effect of hPD-1–IgV on tumor-bearing mice was tested.ResultshPD-1–IgV recombinant protein could bind PD-L1 at molecular and cellular levels and enhance Cytotoxic T Lymphocyte (CTL) activity and anti-tumor effect on tumor-bearing mice in vivo. The percentage of CD4+CD25+ T cells in tumor-bearing mice was decreased compared with control mice after administration of the recombinant protein.DiscussionOur results suggest that inhibition of the interaction between PD-1 and PD-L1 by hPD-1–IgV may be a promising strategy for specific tumor immunotherapy.