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Infusion of Melan-A/Mart-1 specific tumor-infiltrating lymphocytes enhanced relapse-free survival of melanoma patients

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Abstract

Adoptive therapy of cancer has been mostly tested in advanced cancer patients using tumor-infiltrating lymphocytes (TIL). Following discouraging results likely due to poor tumor-specificity of TIL and/or high tumor burden, recent studies reiterate the enormous potential of this therapy, particularly in melanoma. We had performed a phase II/III randomised trial on 88 stage III melanoma patients, who received autologous TIL plus IL-2 or IL-2 alone, after complete tumour resection. We reported previously clinical and immunological results supporting the ability of tumor reactive TIL infusion to prevent further development of the melanoma disease and to increase overall survival of patients bearing only one tumor invaded lymph node. The absence of correlation between overall and disease-free survival and the amount of infused tumor-specific TIL suggested that therapeutic efficiency might depend on other parameters such as antigen specificity, function or persistence of TIL. Here we studied the recognition of a panel of 38 shared tumor-associated antigens (TAA) by TIL infused to the patients included in this assay, in order to determine if treatment outcome could correlate with particular antigen specificities of infused TIL. Results show that the infusion of Melan-A/MART-1 reactive TIL appears to be associated with a longer relapse-free survival for HLA-A2 patients. These results further support the relevance of Melan-A/MART-1 antigen as a prime target for immunotherapy protocols in melanoma.

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Acknowledgments

This work was supported by grants from the “Ligue Nationale contre le Cancer”, the “INSERM” and by a grant from ENACT proposal number 503306. We thank Dr. Rivain-Sebille for her help in the statistical analysis of the data.

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Authors and Affiliations

  1. INSERM U601, 9 quai Moncousu, 44093, Nantes Cedex 1, France

    Houssem Benlalam, Virginie Vignard, Amir Khammari, Annabelle Bonnin, Yann Godet, Francine Jotereau, Brigitte Dreno & Nathalie Labarrière

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

    Amir Khammari & Brigitte Dreno

  3. CHU of Nantes, Unit of cell and gene therapy, 44093, Nantes, France

    Marie-Christine Pandolfino & Brigitte Dreno

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

    Francine Jotereau

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  1. Houssem Benlalam
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  2. Virginie Vignard
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  9. Nathalie Labarrière
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Correspondence to Francine Jotereau or Nathalie Labarrière.

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Benlalam, H., Vignard, V., Khammari, A. et al. Infusion of Melan-A/Mart-1 specific tumor-infiltrating lymphocytes enhanced relapse-free survival of melanoma patients. Cancer Immunol Immunother 56, 515–526 (2007). https://doi.org/10.1007/s00262-006-0204-0

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  • DOI: https://doi.org/10.1007/s00262-006-0204-0

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