Clinical Cancer Research  Infection and Cancer: Biology, Therapeutics, and Prevention
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Clinical Cancer Research Vol. 12, 1921-1927, March 2006
© 2006 American Association for Cancer Research


Cancer Therapy: Preclinical

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 Hasegawa1,2, Yuji Noguchi1, Fumihito Koizumi1, Akiko Uenaka1, Motoyuki Tanaka1, Michihide Shimono1, Hideo Nakamura3, Hiroshi Shiku4, Sacha Gnjatic5, Roger Murphy6, Yuji Hiramatsu2, Lloyd J. Old5 and Eiichi Nakayama1

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{gamma} 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{gamma}.

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.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2006 by the American Association for Cancer Research.