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

Kosei Hasegawa, Yuji Noguchi, Fumihito Koizumi, Akiko Uenaka, Motoyuki Tanaka, Michihide Shimono, Hideo Nakamura, Hiroshi Shiku, Sacha Gnjatic, Roger Murphy, Yuji Hiramatsu, Lloyd J. Old, Eiichi Nakayama

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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 IFNγ 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 IFNγ 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-1157-165, 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-137.50. Conclusions: These findings indicate that CHP/ESO is a promising polyvalent cancer vaccine targeting NY-ESO-1.

Original languageEnglish
Pages (from-to)1921-1927
Number of pages7
JournalClinical Cancer Research
Volume12
Issue number6
DOIs
Publication statusPublished - Mar 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hasegawa, K., Noguchi, Y., Koizumi, F., Uenaka, A., Tanaka, M., Shimono, M., Nakamura, H., Shiku, H., Gnjatic, S., Murphy, R., Hiramatsu, Y., Old, L. J., & Nakayama, E. (2006). 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. Clinical Cancer Research, 12(6), 1921-1927. https://doi.org/10.1158/1078-0432.CCR-05-1900