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Cancer Therapy: Preclinical |
Authors' Affiliations: Departments of 1 Immunology and 2 Obstetrics and Gynecology, Okayama University Graduate School of Medicine and Dentistry, Okayama, 3 Yokohama Research Center, Mitsubishi Welpharma, Yokohama, 4 Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan, 5 Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, and 6 Austin and Repatriation Medical Center, Melbourne, Australia
Requests for reprints: Yuji Noguchi, Department of Immunology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan. Phone: 81-86-235-7192; Fax: 81-86-235-7193; E-mail: noguchi{at}md.okayama-u.ac.jp.
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 IFN
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 IFN
.
Results: NY-ESO-1specific 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-A2binding CD8 T cell epitope. NY-ESO-1 CD4 T cells were Th1-type. We identified a new HLA-DR15binding 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.
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