In vitroStimulation 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
| Autor: | Yuji Noguchi, Lloyd J. Old, Eiichi Nakayama, Motoyuki Tanaka, Kosei Hasegawa, Sacha Gnjatic, Hideo Nakamura, Akiko Uenaka, Fumihito Koizumi, Hiroshi Shiku, Roger Murphy, Yuji Hiramatsu, Michihide Shimono |
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| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Molecular Sequence Data Epitopes T-Lymphocyte Enzyme-Linked Immunosorbent Assay CD8-Positive T-Lymphocytes Epitope Interferon-gamma Interleukin 21 Antigens Neoplasm Cell Line Tumor Humans Cytotoxic T cell Amino Acid Sequence IL-2 receptor Antigen-presenting cell Glucans HLA-DR Serological Subtypes Antigen Presentation Binding Sites CD40 biology Membrane Proteins Dendritic Cells HLA-DR Antigens Natural killer T cell Coculture Techniques Cholesterol Oncology biology.protein Interleukin 12 Cancer research Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Clinical Cancer Research. 12:1921-1927 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-05-1900 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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