Regulating immunity and inhibiting tumor growth by the recombinant peptide sPD-1-CH50.
BACKGROUND
Soluble programmed death-1 (sPD-1) has been proven to bind PD-1 ligands (PD-Ls), block PD-L/PD-1 interactions, and enhance the cytolysis of cytotoxic T-lymphocytes (CTLs). CH50, a two-domain molecule of fibronectin, has been shown to suppress the development of tumors via enhancing the activity of macrophages. This study evaluated the influence of the recombinant peptide sPD-1-CH50 on antitumor immunity.


METHODS
A secretory recombinant peptide, sPD-1-CH50, containing three functional domains was constructed, and its antitumor effect and mechanism were studied.


RESULTS
The data demonstrated that sPD-1-CH50 was able to increase the cytolytic activity of both macrophages and CTLs, especially towards B7-H1-positive tumor cells. The effect correlated with the enhanced production of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). In vivo studies showed that sPD-1-CH50 inhibited the invasiveness and growth of hepatoma.


CONCLUSIONS
Regulation of immune cells by sPD-1-CH50 has potential therapeutic value for the inhibition of invasion and growth of hepatoma.
Qiu
Hui
H
Department of Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, P.R. of China. qiuhui1999@163.com
Liu
Shaoping
S
Xie
Conghua
C
Long
Jian
J
Feng
Zuohua
Z
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D002478:Cells, Cultured; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D007109:Immunity; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C478562:CH50 recombinant polypeptide; D005353:Fibronectins; C491383:Pdcd1 protein, mouse; D010446:Peptide Fragments; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II