Regulating immunity and inhibiting tumor growth by the recombinant peptide sPD-1-CH50

Anticancer Res. 2009 Dec;29(12):5089-94.

Abstract

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.

Materials and 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.

Conclusion: Regulation of immune cells by sPD-1-CH50 has potential therapeutic value for the inhibition of invasion and growth of hepatoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / therapy*
  • Cells, Cultured
  • Cricetinae
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibronectins / genetics
  • Fibronectins / metabolism*
  • Genetic Therapy
  • Immunity
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / immunology*
  • Liver Neoplasms, Experimental / therapy*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • CH50 recombinant polypeptide
  • Fibronectins
  • Pdcd1 protein, mouse
  • Peptide Fragments
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase Type II