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High Avidity Melanoma-reactive Cytotoxic T Lymphocytes Are Efficiently Induced from Peripheral Blood Lymphocytes on Stimulation by Peptide-pulsed Melanoma Cells

Abstract : To design an efficient procedure to expand high avidity melanoma reactive T cells and to perform immunotherapies, we compared conditions of peripheral blood lymphocyte (PBL) stimulation by Melan-A/MART-1 peptides. Avidity of induced CTLs was evaluated by measuring their lysis and cytokine secretion to peptide-pulsed transporter-associated protein-deficient cells and to melanoma cells. In side-by-side experiments, we show that melanoma cells, either allogeneic or autologous, induced the growth of high avidity Melan-A-reactive CTLs from all donors, whereas essentially low avid-ity T cells were induced by peptide-pulsed PBLs. We also show that at least two cytokines, interleukin-6 and interleu-kin-2, were required to promote the growth of high avidity CTLs. Once sorted by tetramer labeling or cloning, the specificity and reactivity to tumor cells of peptide-specific T cells induced by allogeneic melanoma cells were confirmed. We then describe a relatively simple and efficient procedure that allowed us to obtain systematically high amounts (in the range of billion) of high avidity Melan-A/ MART-1-specific T cells from the PBLs of HLA-A2 mela-noma patients and healthy donors in 3 months. Because this antigen is expressed by most melanoma tumors, this procedure should be useful for checking the efficiency of adoptive immunotherapy of melanoma tumors and using functionally well-defined Melan-A/MART-1-specific CTLs in a large group of patients.
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https://www.hal.inserm.fr/inserm-02482162
Contributor : Nathalie Labarriere <>
Submitted on : Monday, February 17, 2020 - 7:24:26 PM
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  • HAL Id : inserm-02482162, version 1
  • PUBMED : 10778978

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Nadine Gervois, Nathalie Labarrière, Soizic Le Guiner, Marie-Christine Pandolfino, Jean-François Fonteneau, et al.. High Avidity Melanoma-reactive Cytotoxic T Lymphocytes Are Efficiently Induced from Peripheral Blood Lymphocytes on Stimulation by Peptide-pulsed Melanoma Cells. Clinical Cancer Research, American Association for Cancer Research, 2000. ⟨inserm-02482162⟩

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