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Analysis of a rare melanoma patient with a spontaneous CTL response to a MAGE-A3 peptide presented by HLA-A1

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Abstract

We describe an HLA-A1 melanoma patient who has mounted a spontaneous cytolytic T cell (CTL) response against an antigenic peptide encoded by gene MAGE-A3 and presented by HLA-A1. The frequency of anti-MAGE-3.A1 CTLp was 5×10−7 of the blood CD8 cells, with a dominant clonotype which was present in six out of seven independent anti-MAGE-3.A1 CTL clones. After vaccination with a recombinant poxvirus coding for the MAGE-3.A1 antigen, the blood frequency of anti-MAGE-3.A1 CTLp increased tenfold. Twenty-two independent CTL clones were derived. Surprisingly, only one of them corresponded to the dominant clonotype present before vaccination. Two new clonotypes were repeated 12 and 7 times, respectively. Our interpretation of these results is that the spontaneous anti-MAGE-3.A1 CTL response pre-existing to vaccination was polyclonal, and that the vaccine restimulated only some of these clones. To estimate the incidence of spontaneous anti-MAGE-3.A1 CTL responses in melanoma patients with a tumor expressing gene MAGE-A3, we measured the blood frequency of anti-MAGE-3.A1 T cells in 45 patients, and found only two clear responses.

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Abbreviations

CTL:

Cytolytic T lymphocytes

MLPC:

Mixed lymphocyte peptide culture

TCR:

T cell receptor

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Acknowledgements

This work was supported by the Belgian Programme on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister’s Office, Science Policy Programming, and by grants from the Fonds J. Maisin (Belgium), the Fédération Belge contre le Cancer (Belgium), the Fondation Salus Sanguinis (Belgium), and the Fonds National de la Recherche Scientifique (Belgium).

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Authors and Affiliations

  1. Christian de Duve Institute of Cellular Pathology, University of Louvain, Avenue Hippocrate 74, UCL 7459, 1200, Brussels, Belgium

    Takeshi Hanagiri, Nicolas van Baren, Thierry Boon & Pierre G. Coulie

  2. The Second Department of Surgery, University of Occupational and Environmental Health, 807-8555, Kitakyushu, Japan

    Takeshi Hanagiri

  3. Brussels Branch, Ludwig Institute for Cancer Research, 1200, Brussels, Belgium

    Nicolas van Baren & Thierry Boon

  4. Department of Medical Oncology, Medical School of the Vrije Universiteit Brussel, 1090, Brussels, Belgium

    Bart Neyns

Authors
  1. Takeshi Hanagiri
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  2. Nicolas van Baren
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  3. Bart Neyns
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  4. Thierry Boon
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  5. Pierre G. Coulie
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Corresponding author

Correspondence to Pierre G. Coulie.

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Hanagiri, T., van Baren, N., Neyns, B. et al. Analysis of a rare melanoma patient with a spontaneous CTL response to a MAGE-A3 peptide presented by HLA-A1. Cancer Immunol Immunother 55, 178–184 (2006). https://doi.org/10.1007/s00262-005-0063-0

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  • DOI: https://doi.org/10.1007/s00262-005-0063-0

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