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A new tyrosinase epitope recognized in the HLA-B*4002 context by CTL from melanoma patients

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Abstract

Melanoma reactive CTL were obtained by stimulating PBL from a melanoma patient in remission since 1994 following adjuvant TIL immunotherapy, with the autologous melanoma cell line. They were cloned by limiting dilution. One CTL clone recognized melanoma cell lines expressing tyrosinase and the B*4002 molecule, either spontaneously or upon transfection. We demonstrated that this clone recognizes the tyrosinase-derived nonapeptide 316-324 (ADVEFCLSL) and the overlapping decapeptide 315–324 (SADVEFCLSL). We derived two distinct additional specific CTL clones from this same patient that were also reactive against B*4002 melanoma cell lines, suggesting a relative diversity of this specific repertoire in this patient. Stimulating PBMC derived from four additional B*4002 melanoma patients with the tyrosinase 316–324 nonapeptide induced the growth of specific cells for two of the patients, demonstrating the immunogenicity of this new epitope. Our data show that this nonapeptide is a new tool that could be used to generate melanoma-specific T cells for adoptive immunotherapy or serve as a peptide vaccine for HLA-B*4002 melanoma patients.

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Acknowledgments

This work was supported by grants from the “Ligue Nationale contre le Cancer and Comite 44”, the “INSERM” and by a grant from ENACT network number 503306. We acknowledge Profs. F. Lang and R. Breathnach for carefully reading the manuscript and Prof. P. Coulie for sending us melanoma patient PBMC.

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Authors and Affiliations

  1. INSERM U892, 9 quai Moncousu, 44093, Nantes cedex 1, France

    Yann Godet, Annabelle Bonnin, Yannik Guilloux, Virginie Vignard, Brigitte Dreno, Francine Jotereau & Nathalie Labarriere

  2. CHU of Nantes, Unit of Skin Cancer, 44093, Nantes, France

    Brigitte Dreno

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

    Yannik Guilloux & Francine Jotereau

  4. Skin Cancer Unit, German Cancer Research Center and University Hospital Mannheim, 68135, Mannheim, Germany

    Dirk Schadendorf

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  1. Yann Godet
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Correspondence to Nathalie Labarriere.

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Godet, Y., Bonnin, A., Guilloux, Y. et al. A new tyrosinase epitope recognized in the HLA-B*4002 context by CTL from melanoma patients. Cancer Immunol Immunother 58, 271–280 (2009). https://doi.org/10.1007/s00262-008-0551-0

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