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In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells
Hematopoietic stem cell transplantation (HSCT) using unrelated cord blood (CB) donors is a suitable approach when an HLA-matched donor is not available. However, one important drawback is the risk of life-threatening viral infections prior to immune reconstitution, particularly from adenoviruses (Ad...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357851/ https://www.ncbi.nlm.nih.gov/pubmed/30740473 http://dx.doi.org/10.1016/j.omtm.2018.12.010 |
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author | Kuranda, Klaudia Caillat-Zucman, Sophie You, Sylvaine Mallone, Roberto |
author_facet | Kuranda, Klaudia Caillat-Zucman, Sophie You, Sylvaine Mallone, Roberto |
author_sort | Kuranda, Klaudia |
collection | PubMed |
description | Hematopoietic stem cell transplantation (HSCT) using unrelated cord blood (CB) donors is a suitable approach when an HLA-matched donor is not available. However, one important drawback is the risk of life-threatening viral infections prior to immune reconstitution, particularly from adenoviruses (AdVs). Although adoptive therapy with ex vivo expanded virus-reactive donor T cells has proven effective to treat these infections in HSCT recipients, the manufacturing process is complex and requires large numbers of cells, which is incompatible with CB donor units. Here, we have adapted our previous accelerated co-cultured dendritic cell (acDC) method, which allows to efficiently and rapidly expand peripheral blood T cells reactive to a given antigen, for use on limited CB material. Selected cytokine cocktails induced DC differentiation and maturation from unfractionated CB mononuclear cell cultures and simultaneously stimulated and expanded, within 10 days, functional CD8(+) T cells specific for the model antigen MelanA or AdV immunodominant peptides. In addition, the use of G-Rex cultures yielded numbers of AdV-reactive CD8(+) T cells compatible with adoptive cell therapy applications. Our acDC strategy, which uses reagents compatible with good manufacturing practices, may be promptly translated into the clinic for treating intercurrent infections in CB HSCT recipients. |
format | Online Article Text |
id | pubmed-6357851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-63578512019-02-08 In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells Kuranda, Klaudia Caillat-Zucman, Sophie You, Sylvaine Mallone, Roberto Mol Ther Methods Clin Dev Article Hematopoietic stem cell transplantation (HSCT) using unrelated cord blood (CB) donors is a suitable approach when an HLA-matched donor is not available. However, one important drawback is the risk of life-threatening viral infections prior to immune reconstitution, particularly from adenoviruses (AdVs). Although adoptive therapy with ex vivo expanded virus-reactive donor T cells has proven effective to treat these infections in HSCT recipients, the manufacturing process is complex and requires large numbers of cells, which is incompatible with CB donor units. Here, we have adapted our previous accelerated co-cultured dendritic cell (acDC) method, which allows to efficiently and rapidly expand peripheral blood T cells reactive to a given antigen, for use on limited CB material. Selected cytokine cocktails induced DC differentiation and maturation from unfractionated CB mononuclear cell cultures and simultaneously stimulated and expanded, within 10 days, functional CD8(+) T cells specific for the model antigen MelanA or AdV immunodominant peptides. In addition, the use of G-Rex cultures yielded numbers of AdV-reactive CD8(+) T cells compatible with adoptive cell therapy applications. Our acDC strategy, which uses reagents compatible with good manufacturing practices, may be promptly translated into the clinic for treating intercurrent infections in CB HSCT recipients. American Society of Gene & Cell Therapy 2018-12-31 /pmc/articles/PMC6357851/ /pubmed/30740473 http://dx.doi.org/10.1016/j.omtm.2018.12.010 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Kuranda, Klaudia Caillat-Zucman, Sophie You, Sylvaine Mallone, Roberto In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells |
title | In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells |
title_full | In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells |
title_fullStr | In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells |
title_full_unstemmed | In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells |
title_short | In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells |
title_sort | in vitro expansion of anti-viral t cells from cord blood by accelerated co-cultured dendritic cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357851/ https://www.ncbi.nlm.nih.gov/pubmed/30740473 http://dx.doi.org/10.1016/j.omtm.2018.12.010 |
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