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A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications
Adoptive cell therapy of donor-derived, antigen-specific T cells expressing native T cell receptors (TCRs) is a powerful strategy to fight viral infections in immunocompromised patients. Determining the fate of T cells following patient infusion hinges on the ability to track them in vivo. While thi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336339/ https://www.ncbi.nlm.nih.gov/pubmed/37448595 http://dx.doi.org/10.1016/j.omtm.2023.06.007 |
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author | Palianina, Darya Di Roberto, Raphaël B. Castellanos-Rueda, Rocío Schlatter, Fabrice Reddy, Sai T. Khanna, Nina |
author_facet | Palianina, Darya Di Roberto, Raphaël B. Castellanos-Rueda, Rocío Schlatter, Fabrice Reddy, Sai T. Khanna, Nina |
author_sort | Palianina, Darya |
collection | PubMed |
description | Adoptive cell therapy of donor-derived, antigen-specific T cells expressing native T cell receptors (TCRs) is a powerful strategy to fight viral infections in immunocompromised patients. Determining the fate of T cells following patient infusion hinges on the ability to track them in vivo. While this is possible by genetic labeling of parent cells, the applicability of this approach has been limited by the non-specificity of the edited T cells. Here, we devised a method for CRISPR-targeted genome integration of a barcoded gene into Epstein-Barr virus-antigen-stimulated T cells and demonstrated its use for exclusively identifying expanded virus-specific cell lineages. Our method facilitated the enrichment of antigen-specific T cells, which then mediated improved cytotoxicity against Epstein-Barr virus-transformed target cells. Single-cell and deep sequencing for lineage tracing revealed the expansion profile of specific T cell clones and their corresponding gene expression signature. This approach has the potential to enhance the traceability and the monitoring capabilities during immunotherapeutic T cell regimens. |
format | Online Article Text |
id | pubmed-10336339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-103363392023-07-13 A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications Palianina, Darya Di Roberto, Raphaël B. Castellanos-Rueda, Rocío Schlatter, Fabrice Reddy, Sai T. Khanna, Nina Mol Ther Methods Clin Dev Original Article Adoptive cell therapy of donor-derived, antigen-specific T cells expressing native T cell receptors (TCRs) is a powerful strategy to fight viral infections in immunocompromised patients. Determining the fate of T cells following patient infusion hinges on the ability to track them in vivo. While this is possible by genetic labeling of parent cells, the applicability of this approach has been limited by the non-specificity of the edited T cells. Here, we devised a method for CRISPR-targeted genome integration of a barcoded gene into Epstein-Barr virus-antigen-stimulated T cells and demonstrated its use for exclusively identifying expanded virus-specific cell lineages. Our method facilitated the enrichment of antigen-specific T cells, which then mediated improved cytotoxicity against Epstein-Barr virus-transformed target cells. Single-cell and deep sequencing for lineage tracing revealed the expansion profile of specific T cell clones and their corresponding gene expression signature. This approach has the potential to enhance the traceability and the monitoring capabilities during immunotherapeutic T cell regimens. American Society of Gene & Cell Therapy 2023-06-19 /pmc/articles/PMC10336339/ /pubmed/37448595 http://dx.doi.org/10.1016/j.omtm.2023.06.007 Text en © 2023 The Author(s) https://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 | Original Article Palianina, Darya Di Roberto, Raphaël B. Castellanos-Rueda, Rocío Schlatter, Fabrice Reddy, Sai T. Khanna, Nina A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications |
title | A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications |
title_full | A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications |
title_fullStr | A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications |
title_full_unstemmed | A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications |
title_short | A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications |
title_sort | method for polyclonal antigen-specific t cell-targeted genome editing (target) for adoptive cell transfer applications |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336339/ https://www.ncbi.nlm.nih.gov/pubmed/37448595 http://dx.doi.org/10.1016/j.omtm.2023.06.007 |
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