Melanoma patients respond to a new HLA-A*01-presented antigenic ligand derived from a multi-epitope region of melanoma antigen TRP-2

Authors

  • Annette Paschen,

    Corresponding author
    1. Skin Cancer Unit of the German Cancer Research Center at the University Hospital of Mannheim, Mannheim, Germany
    • University Hospital Mannheim, Skin Cancer Unit of the German Cancer Research Center Heidelberg (Dermato-Oncology), House 24, Theodor Kutzer Ufer 1, 68135 Mannheim, Germany
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    • The first two authors contributed equally to this study.

    • Fax: +49-621-383-2163.

  • Weiqing Jing,

    1. Skin Cancer Unit of the German Cancer Research Center at the University Hospital of Mannheim, Mannheim, Germany
    2. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
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    • The first two authors contributed equally to this study.

  • Ingo Drexler,

    1. GSF-Institute for Molecular Virology and Institute for Virology, Technical University of Munich, Munich, Germany
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  • Moritz Klemm,

    1. GSF-Institute for Molecular Virology and Institute for Virology, Technical University of Munich, Munich, Germany
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  • Mingxia Song,

    1. Skin Cancer Unit of the German Cancer Research Center at the University Hospital of Mannheim, Mannheim, Germany
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  • Jan Müller-Berghaus,

    1. Skin Cancer Unit of the German Cancer Research Center at the University Hospital of Mannheim, Mannheim, Germany
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  • Xuan Duc Nguyen,

    1. Institute of Transfusion Medicine and Immunology, Mannheim, Germany
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  • Wolfram Osen,

    1. Skin Cancer Unit of the German Cancer Research Center at the University Hospital of Mannheim, Mannheim, Germany
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  • Stefan Stevanovic,

    1. Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany
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  • Gerd Sutter,

    1. GSF-Institute for Molecular Virology and Institute for Virology, Technical University of Munich, Munich, Germany
    2. Department of Virology, Paul-Ehrlich-Institute, Langen, Germany
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  • Dirk Schadendorf

    1. Skin Cancer Unit of the German Cancer Research Center at the University Hospital of Mannheim, Mannheim, Germany
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Abstract

Tyrosinase-related protein-2 (TRP-2) is a known target antigen of spontaneous cytotoxic T cell responses in melanoma patients. Its frequent expression in metastatic tumors suggests that it might be an ideal candidate antigen for T cell-based immunotherapy. To provide knowledge about TRP-2-derived T cell epitopes useful for immunotherapy we applied a “reverse immunology strategy” based on repeated in vitro peptide stimulation of peripheral blood lymphocytes (PBL) from normal donors with predicted HLA-A*01 ligands. This led to the identification of TRP-2181–190 as the first HLA-A*01-presented TRP-2-derived epitope. T-cell lines specific for peptide TRP-2181–190 could be established from PBL of 50% of the normal HLA-A*01+ donors tested. Such T cells responded specifically to autologous dendritic cells transduced virally with TRP-2, as well as to HLA-A*01+, TRP-2+ melanoma cells, although tumor cells had to be pretreated with IFN-γ to become susceptible to T cell recognition. Interestingly, short-term in vitro peptide stimulation of PBL from HLA-A*01+ melanoma patients showed the presence of TRP-2181–190-reactive CD8+ T cells in some donors, suggesting their in vivo sensitization. Because TRP-2181–190 overlaps with the known HLA-A*0201-presented epitope TRP-2180–188, an 11mer peptide encompassing both epitopes might be of specific value for vaccination of a broad population of melanoma patients. © 2005 Wiley-Liss, Inc.

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