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

Journal: Clinical cancer research : an official journal of the American Association for Cancer Research 2006;12(6):1921-7

PMID: 16551878

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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 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.

Address: Department of Immunology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.

DOI: 10.1158/1078-0432.CCR-05-1900