Abstract
There remains a need to identify novel epitopes of potential tumour target antigens for use in immunotherapy of cancer. Here, several melanoma tissues and cell lines but not normal tissues were found to overexpress the cancer-testis antigen HAGE at the mRNA and protein level. We identified a HAGE-derived 15-mer peptide containing a shorter predicted MHC class I-binding sequence within a class II-binding sequence. However, only the longer peptide was found to be both endogenously processed and immunogenic for T cells in transgenic mice in vivo, as well as for human T cells in vitro. A different class I-binding peptide, not contained within a longer class II sequence, was subsequently found to be both immunogenic and endogenously processed in transgenic mice, as was a second class II epitope. These novel HAGE-derived epitopes may contribute to the range of immunotherapeutic targets for use in cancer vaccination programs.
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Acknowledgments
This work was supported by European Commission Contracts LSHC-CT-2004-503306 (ENACT) and ESTDAB (QLRI-CT-2000-01325), the John and Lucille van Geest Foundation and the Deutsche Forschungsgemeinschaft (DFG-SFB-685-B4). We are also grateful to Robert Davy, Stephen Reeder and Lilly Wedel for excellent technical support.
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M.G. Mathieu and A.J. Knights are joint first authors and have contributed equally to this paper.
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Mathieu, M.G., Knights, A.J., Pawelec, G. et al. HAGE, a cancer/testis antigen with potential for melanoma immunotherapy: identification of several MHC class I/II HAGE-derived immunogenic peptides. Cancer Immunol Immunother 56, 1885–1895 (2007). https://doi.org/10.1007/s00262-007-0331-2
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DOI: https://doi.org/10.1007/s00262-007-0331-2