Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / therapeutic use*
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Antigens, Differentiation / immunology*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / therapeutic use*
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B7-1 Antigen / immunology
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B7-H1 Antigen
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Cell Line, Tumor
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Humans
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Immunoglobulin Variable Region / genetics
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Immunoglobulin Variable Region / therapeutic use*
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Immunotherapy
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Membrane Glycoproteins / antagonists & inhibitors*
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Membrane Glycoproteins / immunology
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Mice
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Neoplasms / therapy*
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Peptides / antagonists & inhibitors*
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Peptides / immunology
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Programmed Cell Death 1 Receptor
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / therapeutic use*
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T-Lymphocytes, Cytotoxic*
Substances
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Antigens, CD
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Antigens, Differentiation
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Apoptosis Regulatory Proteins
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B7-1 Antigen
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B7-H1 Antigen
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Cd274 protein, mouse
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Immunoglobulin Variable Region
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Membrane Glycoproteins
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PDCD1 protein, human
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Pdcd1 protein, mouse
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Peptides
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Programmed Cell Death 1 Receptor
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Recombinant Fusion Proteins