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Lack of tumor recognition by cytolytic T lymphocyte clones recognizing peptide 195–203 encoded by gene MAGE-A3 and presented by HLA-A24 molecules

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Abstract

Gene MAGE-A3 encodes tumor-specific antigenic peptides recognized by T cells on many tumors. MAGE-A3 peptides presented by HLA class I molecules have been identified using CD8 lymphocytes stimulated with cells that either expressed gene MAGE-A3 or were pulsed with candidate peptides. One antigen identified with the latter method is peptide MAGE-A3195–203 IMPKAGLLI, presented by HLA-A24 molecules. It has been used to vaccinate advanced cancer patients. Here, we have used HLA/peptide tetramers to detect T cells recognizing this peptide. Their frequency was estimated to be 2 × 10−8 of the blood CD8 cells in non-cancerous HLA-A24+ individuals, which is tenfold lower than the reported frequencies of T cells against other MAGE peptides. In the blood of a patient vaccinated with MAGE-A3, the estimated frequency was 5 × 10−7. Anti-MAGE-3.A24 cytolytic T cell clones were derived, that lysed peptide-pulsed cells with half-maximal effect at the low concentration of 500 pM. However, these CTL did not recognize a panel of HLA-A24+ tumor cells that expressed MAGE-A3 at levels similar to those found in HLA-A1+ tumor cells recognized by anti-MAGE-3.A1 CTLs. Furthermore, 293-EBNA cells transfected with MAGE-A3 and HLA-A24 constructs were hardly recognized by the anti-MAGE-3.A24 CTL clones. These results suggest that peptide MAGE-A3195–203 is poorly processed and is not an appropriate target for cancer immunotherapy.

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Abbreviations

CTL:

Cytolytic T lymphocytes

DC:

Dendritic cells

EBV:

Epstein-Barr virus

MLPC:

Mixed lymphocyte peptide culture

PBMC:

Peripheral blood mononuclear cells

TCR:

T cell receptor

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Acknowledgments

We thank Therèse Aerts for expert technical assistance, André Tonon for cell sorting experiments, and Suzanne Depelchin for editorial help. This work was supported by the Belgian Programme on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister’s Office, Science Policy Programing, and by grants from the Fonds J. Maisin (Belgium), the Fondation contre le Cancer (Belgium), the Fondation Salus Sanguinis (Belgium), the Fonds National de la Recherche Scientifique (Belgium) and the FB Assurances and VIVA (Belgium).

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Authors and Affiliations

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

    Tomoko So, Jacques Chapiro, Didier Colau, Francis Brasseur, Thierry Boon & Pierre G. Coulie

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

    Tomoko So, Takeshi Hanagiri & Kosei Yasumoto

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

    Jacques Chapiro, Didier Colau, Francis Brasseur & Thierry Boon

Authors
  1. Tomoko So
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  2. Takeshi Hanagiri
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  3. Jacques Chapiro
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  4. Didier Colau
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  5. Francis Brasseur
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  6. Kosei Yasumoto
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  7. Thierry Boon
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  8. Pierre G. Coulie
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Correspondence to Pierre G. Coulie.

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So, T., Hanagiri, T., Chapiro, J. et al. Lack of tumor recognition by cytolytic T lymphocyte clones recognizing peptide 195–203 encoded by gene MAGE-A3 and presented by HLA-A24 molecules. Cancer Immunol Immunother 56, 259–269 (2007). https://doi.org/10.1007/s00262-006-0186-y

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  • DOI: https://doi.org/10.1007/s00262-006-0186-y

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