In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein: Identification of a new HLA-DR15-binding CD4 T-cell epitope

Clin Cancer Res. 2006 Mar 15;12(6):1921-7. doi: 10.1158/1078-0432.CCR-05-1900.

Abstract

Purpose: NY-ESO-1 belongs to a class of cancer/testis antigens and has been shown to be immunogenic in cancer patients. We synthesized a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP/ESO) and investigated the in vitro stimulation of CD8 and CD4 T cells from peripheral blood mononuclear cells in healthy donors with autologous CHP/ESO-loaded dendritic cells as antigen-presenting cells.

Experimental design: In vitro stimulation of CD8 or CD4 T cells was determined by IFNgamma ELISPOT assays against autologous EBV-B cells infected with vaccinia/NY-ESO-1 recombinant virus or wild-type vaccinia virus as targets and by ELISA measuring secreted IFNgamma.

Results: NY-ESO-1-specific CD8 and CD4 T cells were induced. In a donor expressing HLA-A2, CD8 T cells stimulated with CHP/ESO-loaded dendritic cells recognized naturally processed NY-ESO-1(157-165), an HLA-A2-binding CD8 T cell epitope. NY-ESO-1 CD4 T cells were Th1-type. We identified a new HLA-DR15-binding CD4 T cell epitope, NY-ESO-1(37-50).

Conclusions: These findings indicate that CHP/ESO is a promising polyvalent cancer vaccine targeting NY-ESO-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / immunology
  • Binding Sites / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cholesterol / chemistry
  • Coculture Techniques
  • Dendritic Cells / chemistry
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / immunology
  • Glucans / chemistry*
  • Glucans / immunology
  • HLA-DR Antigens / immunology
  • HLA-DR Serological Subtypes
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Interferon-gamma / biosynthesis
  • Membrane Proteins / chemistry*
  • Membrane Proteins / immunology
  • Molecular Sequence Data

Substances

  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Epitopes, T-Lymphocyte
  • Glucans
  • HLA-DR Antigens
  • HLA-DR Serological Subtypes
  • HLA-DR15 antigen
  • Membrane Proteins
  • Interferon-gamma
  • pullulan
  • Cholesterol