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


CONCLUSIONS
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.
Biotechnology Center, The Fourth Military Medical University, Xi'an, People's Republic of China.
C
C
Zhang
S
S
Wu
X
X
Xue
M
M
Li
X
X
Qin
W
W
Li
W
W
Han
Y
Y
Zhang
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000627:therapeutic use*; D000943:Antigens, Differentiation / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000627:therapeutic use*; D018122:B7-1 Antigen / Q000276:immunology; D060890:B7-H1 Antigen; D045744:Cell Line, Tumor; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000627:therapeutic use*; D007167:Immunotherapy; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D011993:Recombinant Fusion Proteins