Research on the epigenetic modification of pancreatic cancer vaccine

Hepatogastroenterology. 2014 Mar-Apr;61(130):272-7.

Abstract

Pancreatic cancer is characterized as a type of gastrointestinal tumor with a poor prognosis and high degree of malignancy. CIITA gene was found highly methylated in pancreatic carcinoma cell line PANC-1 and responsible for the low expression of MHC-II that may lead to immune evasion. Here, we tried to prepare pancreatic cancer vaccine with PANC-1 cells via epigenetic modification to enhance the MHC-II expression. Then the vaccine was injected into C57BL/6J mice and the effect was examined. Our study found that the vaccine could promote the proliferation of antigen-specific T cells, enhance the killing activity of cytotoxic lymphocytes (CTL), promote Th1-type cells mediated secretion of cytokines IFN-gamma and IL-2 while inhibiting Th2-type cells mediated secretion of IL-4, and inhibit the secretion of TGF-beta. Generally, the epigenetically modified vaccine could enhance the body's anti-tumor immune response, providing feasibility research on cancer vaccine for therapy of pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / genetics*
  • Cancer Vaccines / immunology
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / analysis
  • Cytokines / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA Methylation / drug effects
  • DNA Methylation / genetics*
  • Enzyme Inhibitors / pharmacology
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / genetics*
  • Genes, MHC Class II / drug effects
  • Genes, MHC Class II / genetics
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / drug effects
  • Nuclear Proteins / genetics
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology*
  • Spleen / cytology
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism
  • Trans-Activators / drug effects
  • Trans-Activators / genetics

Substances

  • Cancer Vaccines
  • Cytokines
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Trans-Activators
  • DNA (Cytosine-5-)-Methyltransferases