Melanoma patients respond to a new HLA-A*01-presented antigenic ligand derived from a multi-epitope region of melanoma antigen TRP-2
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...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
26 April 2005
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| In: |
International journal of cancer
Year: 2005, Jahrgang: 116, Heft: 6, Pages: 944-948 |
| ISSN: | 1097-0215 |
| DOI: | https://doi.org/10.1002/ijc.21132 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/ijc.21132 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.21132 
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| Verfasserangaben: | Annette Paschen, Weiqing Jing, Ingo Drexler, Moritz Klemm, Mingxia Song, Jan Müller‐Berghaus, Xuan Duc Nguyen, Wolfram Osen, Stefan Stevanovic, Gerd Sutter and Dirk Schadendorf |
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| 245 | 1 | 0 | |a Melanoma patients respond to a new HLA-A*01-presented antigenic ligand derived from a multi-epitope region of melanoma antigen TRP-2 |c Annette Paschen, Weiqing Jing, Ingo Drexler, Moritz Klemm, Mingxia Song, Jan Müller‐Berghaus, Xuan Duc Nguyen, Wolfram Osen, Stefan Stevanovic, Gerd Sutter and Dirk Schadendorf |
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| 520 | |a 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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