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

Cytotherapy. 2008;10(7):711-9. doi: 10.1080/14653240802320237.


Background: Blockade 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.

Methods: The 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.

Results: hPD-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.

Discussion: Our 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / therapeutic use*
  • Antigens, Differentiation / immunology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / therapeutic use*
  • B7-1 Antigen / immunology
  • B7-H1 Antigen
  • Cell Line, Tumor
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / therapeutic use*
  • Immunotherapy
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / immunology
  • Mice
  • Neoplasms / therapy*
  • Peptides / antagonists & inhibitors*
  • Peptides / immunology
  • Programmed Cell Death 1 Receptor
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / therapeutic use*
  • T-Lymphocytes, Cytotoxic*


  • Antigens, CD
  • Antigens, Differentiation
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Immunoglobulin Variable Region
  • Membrane Glycoproteins
  • PDCD1 protein, human
  • Pdcd1 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Receptor
  • Recombinant Fusion Proteins