Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/170103
Title: | Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial |
Author: | Castella, Maria Caballero Baños, Miguel Ortiz-Maldonado Gibson, Valentín González Navarro, Europa Azucena Suñé, Guillermo Antoñana Vildosola, Asier Boronat, Anna Marzal Martí, Berta Millán, Lucía Martín-Antonio, Beatriz Cid Vidal, Joan Lozano, Miquel García, Enric Tabera, Jaime Trias, Esteve Perpiña, Unai Canals i Coll, Josep M. Baumann, Tycho Benítez-Ribas, Daniel Campo Güerri, Elias Yagüe, Jordi Urbano Ispizua, Álvaro Rives, Susana Delgado, Julio (Delgado González) Juan, Manel |
Keywords: | Bioreactors Fenotip Bioreactors Phenotype |
Issue Date: | 20-Mar-2020 |
Publisher: | Frontiers Media |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2020.00482 |
It is part of: | Frontiers in Immunology, 2020, vol. 11, p. 482 |
URI: | http://hdl.handle.net/2445/170103 |
Related resource: | https://doi.org/10.3389/fimmu.2020.00482 |
ISSN: | 1664-3224 |
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 | |
---|---|---|---|---|
702936.pdf | 1.08 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License