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An additional ORF on meloe cDNA encodes a new melanoma antigen, MELOE-2, recognized by melanoma-specific T cells in the HLA-A2 context

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Abstract

We characterized a new melanoma antigen derived from one of the multiple open reading frames (ORFs) of the meloe transcript. The meloe gene is overexpressed in melanomas as compared to other cancer cell lines and normal tissues. The corresponding transcript is rather unusual, in that it does not contain a long unique ORF but multiple short ORFs. We recently characterized a tumor epitope derived from a polypeptide (MELOE-1) encoded by the ORF1230–1370 and involved in relapse prevention of melanoma patients treated with autologous tumor infiltrating lymphocytes (TIL). Here we show that the ORF285–404 encodes a polypeptide called MELOE-2 that also generated a HLA-A2 epitope recognized by a melanoma-specific T cell clone derived from the same TIL population from which we derived the MELOE-1-specific T cell clone. We also showed that HLA-A2 melanoma cells were spontaneously recognized by the MELOE-2-specific T cell clone, and we detected the presence of MELOE-2 reactive T cells in another TIL population infused to a patient who remained relapse-free after TIL treatment. These results demonstrate that translation of meloe transcript in melanoma cells can produce at least two immunogenic polypeptides, MELOE-1 and MELOE-2, from two distinct ORFs that could be relevant target for melanoma immunotherapy.

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Acknowledgments

This work was supported by grants from the “Association pour la Recherche contre le Cancer no. 1074”, and the “INSERM”. Yann Godet was recipient of fellowship awarded by the “Association pour la Recherche contre le Cancer”. We thank the recombinant protein facility and the sequencing facility of the IFR 26 for the production of HLA/peptide complexes and sequencing experiments.

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Authors and Affiliations

  1. CRCNA, Institut de Recherche Therapeutique, Université de Nantes, UMR INSERM U892, 8 Quai Moncousu, BP70721, 44007, Nantes cedex 1, France

    Yann Godet, Agnès Moreau-Aubry, Dimitri Mompelat, Virginie Vignard, Amir Khammari, Brigitte Dreno, Francois Lang, Francine Jotereau & Nathalie Labarriere

  2. Faculté des Sciences, Université de Nantes, 44322, Nantes, France

    Agnès Moreau-Aubry & Francine Jotereau

  3. Unit of Skin Cancer, Centre Hospitalo-Universitaire de Nantes, 44093, Nantes, France

    Amir Khammari & Brigitte Dreno

  4. Université de Nantes, UFR des Sciences Pharmaceutiques, 44322, Nantes, France

    Francois Lang

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  1. Yann Godet
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  2. Agnès Moreau-Aubry
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  9. Nathalie Labarriere
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Correspondence to Nathalie Labarriere.

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Godet, Y., Moreau-Aubry, A., Mompelat, D. et al. An additional ORF on meloe cDNA encodes a new melanoma antigen, MELOE-2, recognized by melanoma-specific T cells in the HLA-A2 context. Cancer Immunol Immunother 59, 431–439 (2010). https://doi.org/10.1007/s00262-009-0762-z

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  • DOI: https://doi.org/10.1007/s00262-009-0762-z

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