Authors: | 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. |
Article Title: | 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 |
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-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. © 2006 American Association for Cancer Research. |
Keywords: | controlled study; human cell; cd8+ t lymphocyte; cd8-positive t-lymphocytes; dendritic cell; membrane proteins; in vitro study; cell line, tumor; wild type; enzyme linked immunosorbent assay; antigen presentation; lymphocyte activation; dendritic cells; amino acid sequence; molecular sequence data; antigens, neoplasm; gamma interferon; ny eso 1 antigen; cd4+ t lymphocyte; cd4-positive t-lymphocytes; hla-dr antigens; epitope; vaccinia virus; protein secretion; pullulan; cholesterol; binding sites; interferon-gamma; virus recombinant; enzyme-linked immunosorbent assay; antigen binding; enzyme linked immunospot assay; epitopes, t-lymphocyte; epstein barr virus; peripheral blood mononuclear cell; hla a2 antigen; coculture techniques; vaccinia; hydrophobic and hydrophilic interactions; hydrophobicity; interferon type ii; glucans; hla dr15 antigen |
Journal Title: | Clinical Cancer Research |
Volume: | 12 |
Issue: | 6 |
ISSN: | 1078-0432 |
Publisher: | American Association for Cancer Research |
Date Published: | 2006-03-15 |
Start Page: | 1921 |
End Page: | 1927 |
Language: | English |
DOI: | 10.1158/1078-0432.ccr-05-1900 |
PUBMED: | 16551878 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 14" - "Export Date: 4 June 2012" - "CODEN: CCREF" - "Source: Scopus" |