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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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Bibliographic Details
Main Authors: Paschen, Annette (Author) , Song, Mingxia (Author) , Nguyen, Xuan-Duc (Author) , Osen, Wolfram (Author) , Schadendorf, Dirk (Author)
Format: Article (Journal)
Language:English
Published: 26 April 2005
In: International journal of cancer
Year: 2005, Volume: 116, Issue: 6, Pages: 944-948
ISSN:1097-0215
DOI:https://doi.org/10.1002/ijc.21132
Online Access: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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Author Notes: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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Summary: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.
Item Description:Gesehen am 05.02.2021
Physical Description:Online Resource
ISSN:1097-0215
DOI:https://doi.org/10.1002/ijc.21132

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