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http://hdl.handle.net/2445/170103
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DC Field | Value | Language |
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dc.contributor.author | Castella, Maria | - |
dc.contributor.author | Caballero Baños, Miguel | - |
dc.contributor.author | Ortiz-Maldonado Gibson, Valentín | - |
dc.contributor.author | González Navarro, Europa Azucena | - |
dc.contributor.author | Suñé, Guillermo | - |
dc.contributor.author | Antoñana Vildosola, Asier | - |
dc.contributor.author | Boronat, Anna | - |
dc.contributor.author | Marzal Martí, Berta | - |
dc.contributor.author | Millán, Lucía | - |
dc.contributor.author | Martín-Antonio, Beatriz | - |
dc.contributor.author | Cid Vidal, Joan | - |
dc.contributor.author | Lozano, Miquel | - |
dc.contributor.author | García, Enric | - |
dc.contributor.author | Tabera, Jaime | - |
dc.contributor.author | Trias, Esteve | - |
dc.contributor.author | Perpiña, Unai | - |
dc.contributor.author | Canals i Coll, Josep M. | - |
dc.contributor.author | Baumann, Tycho | - |
dc.contributor.author | Benítez-Ribas, Daniel | - |
dc.contributor.author | Campo Güerri, Elias | - |
dc.contributor.author | Yagüe, Jordi | - |
dc.contributor.author | Urbano Ispizua, Álvaro | - |
dc.contributor.author | Rives, Susana | - |
dc.contributor.author | Delgado, Julio (Delgado González) | - |
dc.contributor.author | Juan, Manel | - |
dc.date.accessioned | 2020-09-02T12:54:26Z | - |
dc.date.available | 2020-09-02T12:54:26Z | - |
dc.date.issued | 2020-03-20 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | http://hdl.handle.net/2445/170103 | - |
dc.description.abstract | Development of semi-automated devices that can reduce the hands-on time and standardize the production of clinical-grade CAR T-cells, such as CliniMACS Prodigy from Miltenyi, is key to facilitate the development of CAR T-cell therapies, especially in academic institutions. However, the feasibility of manufacturing CAR T-cell products from heavily pre-treated patients with this system has not been demonstrated yet. Here we report and characterize the production of 28 CAR T-cell products in the context of a phase I clinical trial for CD19+ B-cell malignancies (NCT03144583). The system includes CD4-CD8 cell selection, lentiviral transduction and T-cell expansion using IL-7/IL-15. Twenty-seven out of 28 CAR T-cell products manufactured met the full list of specifications and were considered valid products. Ex vivo cell expansion lasted an average of 8.5 days and had a mean transduction rate of 30.6 ± 13.44%. All products obtained presented cytotoxic activity against CD19+ cells and were proficient in the secretion of pro-inflammatory cytokines. Expansion kinetics was slower in patient's cells compared to healthy donor's cells. However, product potency was comparable. CAR T-cell subset phenotype was highly variable among patients and largely determined by the initial product. TCM and TEM were the predominant T-cell phenotypes obtained. 38.7% of CAR T-cells obtained presented a TN or TCM phenotype, in average, which are the subsets capable of establishing a long-lasting T-cell memory in patients. An in-depth analysis to identify individual factors contributing to the optimal T-cell phenotype revealed that ex vivo cell expansion leads to reduced numbers of TN, TSCM, and TEFF cells, while TCM cells increase, both due to cell expansion and CAR-expression. Overall, our results show for the first time that clinical-grade production of CAR T-cells for heavily pre-treated patients using CliniMACS Prodigy system is feasible, and that the obtained products meet the current quality standards of the field. Reduced ex vivo expansion may yield CAR T-cell products with increased persistence in vivo. | - |
dc.format.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2020.00482 | - |
dc.relation.ispartof | Frontiers in Immunology, 2020, vol. 11, p. 482 | - |
dc.relation.uri | https://doi.org/10.3389/fimmu.2020.00482 | - |
dc.rights | cc-by (c) Castella, Maria et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Medicina) | - |
dc.subject.classification | Bioreactors | - |
dc.subject.classification | Fenotip | - |
dc.subject.other | Bioreactors | - |
dc.subject.other | Phenotype | - |
dc.title | Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 702936 | - |
dc.date.updated | 2020-09-02T12:54:26Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32528460 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
Files in This Item:
File | Description | Size | Format | |
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702936.pdf | 1.08 MB | Adobe PDF | View/Open |
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