A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic Melanoma

A number of trials of adoptive transfer of tumor-specific T lymphocytes have been performed in the last 20 years in metastatic melanoma, with increasingly encouraging results as the relevant melanoma antigens were identified and the purity/specificity of injected T cells improved. We have previously...

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Main Authors: N. Labarriere, A. Fortun, A. Bellec, A. Khammari, B. Dreno, S. Saïagh, F. Lang
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2013/932318
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author N. Labarriere
A. Fortun
A. Bellec
A. Khammari
B. Dreno
S. Saïagh
F. Lang
author_facet N. Labarriere
A. Fortun
A. Bellec
A. Khammari
B. Dreno
S. Saïagh
F. Lang
author_sort N. Labarriere
collection DOAJ
description A number of trials of adoptive transfer of tumor-specific T lymphocytes have been performed in the last 20 years in metastatic melanoma, with increasingly encouraging results as the relevant melanoma antigens were identified and the purity/specificity of injected T cells improved. We have previously described a sorting method of epitope-specific T lymphocytes that uses magnetic beads coated with HLA/peptide complexes and we suggested that this method could be applied to a clinical setting. In the present work, we provide a detailed description of the whole GMP process of sorting and amplification of clinical grade T cells specific for the melanoma antigens Melan-A and MELOE-1. All the reagents used in this process including the sorting reagent were produced in GMP conditions and we document the optimization of the different steps of the process such as peptide stimulation, sorting, and amplification. The optimized procedure, validated in 3 blank runs in a clinical setting, allowed the production of at least 108 pure (>90%) Melan-A- and MELOE-1-specific T cells within 28 days starting with 100 mL of blood from metastatic melanoma patients. This GMP process is thus ready to be used in an upcoming phase I/II clinical trial on metastatic melanoma patients.
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language English
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series Clinical and Developmental Immunology
spelling doaj-art-4164e8432cc44aab87290275d34d12a62025-02-03T01:22:16ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/932318932318A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic MelanomaN. Labarriere0A. Fortun1A. Bellec2A. Khammari3B. Dreno4S. Saïagh5F. Lang6Inserm, U892, 44000 Nantes, FranceInserm, U892, 44000 Nantes, FranceUnit of Cell and Gene Therapy, CHU Nantes, 44000 Nantes, FranceInserm, U892, 44000 Nantes, FranceInserm, U892, 44000 Nantes, FranceUnit of Cell and Gene Therapy, CHU Nantes, 44000 Nantes, FranceInserm, U892, 44000 Nantes, FranceA number of trials of adoptive transfer of tumor-specific T lymphocytes have been performed in the last 20 years in metastatic melanoma, with increasingly encouraging results as the relevant melanoma antigens were identified and the purity/specificity of injected T cells improved. We have previously described a sorting method of epitope-specific T lymphocytes that uses magnetic beads coated with HLA/peptide complexes and we suggested that this method could be applied to a clinical setting. In the present work, we provide a detailed description of the whole GMP process of sorting and amplification of clinical grade T cells specific for the melanoma antigens Melan-A and MELOE-1. All the reagents used in this process including the sorting reagent were produced in GMP conditions and we document the optimization of the different steps of the process such as peptide stimulation, sorting, and amplification. The optimized procedure, validated in 3 blank runs in a clinical setting, allowed the production of at least 108 pure (>90%) Melan-A- and MELOE-1-specific T cells within 28 days starting with 100 mL of blood from metastatic melanoma patients. This GMP process is thus ready to be used in an upcoming phase I/II clinical trial on metastatic melanoma patients.http://dx.doi.org/10.1155/2013/932318
spellingShingle N. Labarriere
A. Fortun
A. Bellec
A. Khammari
B. Dreno
S. Saïagh
F. Lang
A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic Melanoma
Clinical and Developmental Immunology
title A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic Melanoma
title_full A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic Melanoma
title_fullStr A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic Melanoma
title_full_unstemmed A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic Melanoma
title_short A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic Melanoma
title_sort full gmp process to select and amplify epitope specific t lymphocytes for adoptive immunotherapy of metastatic melanoma
url http://dx.doi.org/10.1155/2013/932318
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