Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor
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 o...
| Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | article |
| Publication Date: | 2020 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:236426 |
| Online Access: | https://ddd.uab.cat/record/236426 https://dx.doi.org/urn:doi:10.3389/fimmu.2020.00482 |
| Access Level: | Open access |
| Keyword: | Chimeric antigen receptor CD19 Leukemia Lymphoma Immunotherapy CAR T-cell production CliniMACS Prodigy |
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| dc.title.none.fl_str_mv |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor Experience from an academic phase i clinical trial |
| title |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor |
| spellingShingle |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor Castellà, Maria Chimeric antigen receptor CD19 Leukemia Lymphoma Immunotherapy CAR T-cell production CliniMACS Prodigy |
| title_short |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor |
| title_full |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor |
| title_fullStr |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor |
| title_full_unstemmed |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor |
| title_sort |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor |
| dc.creator.none.fl_str_mv |
Castellà, Maria Caballero-Baños, M. Ortiz-Maldonado, Valentín|||0000-0003-4699-6862 González-Navarro, Europa Azucena|||0000-0003-3310-5557 Suñé, Guillermo|||0000-0002-4034-4348 Antoñana Vildosola, Asier|||0000-0002-1404-6398 Boronat Barado, Anna Marzal, Berta Millán, Lucía Martín-Antonio, B.|||0000-0003-0612-2693 Cid Colom, Jordi|||0000-0002-6406-0585 Lozano, Miquel|||0000-0003-2593-833X García, E. Tabera, Jaime|||0000-0002-5430-0151 Trias, E. Perpiña, U. Canals, Josep M.|||0000-0001-6829-7670 Baumann, Tycho|||0000-0003-4421-0088 Benítez Ribas, Daniel|||0000-0002-2346-5324 Campo, Elias|||0000-0001-9850-9793 Yagüe, Jordi|||0000-0001-8210-1929 Urbano Ispizua, Álvaro|||0000-0002-7529-9399 Rives, S. Delgado, Julio|||0000-0002-5157-4376 Juan, Manel|||0000-0002-3064-1648 |
| author |
Castellà, Maria |
| author_facet |
Castellà, Maria Caballero-Baños, M. Ortiz-Maldonado, Valentín|||0000-0003-4699-6862 González-Navarro, Europa Azucena|||0000-0003-3310-5557 Suñé, Guillermo|||0000-0002-4034-4348 Antoñana Vildosola, Asier|||0000-0002-1404-6398 Boronat Barado, Anna Marzal, Berta Millán, Lucía Martín-Antonio, B.|||0000-0003-0612-2693 Cid Colom, Jordi|||0000-0002-6406-0585 Lozano, Miquel|||0000-0003-2593-833X García, E. Tabera, Jaime|||0000-0002-5430-0151 Trias, E. Perpiña, U. Canals, Josep M.|||0000-0001-6829-7670 Baumann, Tycho|||0000-0003-4421-0088 Benítez Ribas, Daniel|||0000-0002-2346-5324 Campo, Elias|||0000-0001-9850-9793 Yagüe, Jordi|||0000-0001-8210-1929 Urbano Ispizua, Álvaro|||0000-0002-7529-9399 Rives, S. Delgado, Julio|||0000-0002-5157-4376 Juan, Manel|||0000-0002-3064-1648 |
| author_role |
author |
| author2 |
Caballero-Baños, M. Ortiz-Maldonado, Valentín|||0000-0003-4699-6862 González-Navarro, Europa Azucena|||0000-0003-3310-5557 Suñé, Guillermo|||0000-0002-4034-4348 Antoñana Vildosola, Asier|||0000-0002-1404-6398 Boronat Barado, Anna Marzal, Berta Millán, Lucía Martín-Antonio, B.|||0000-0003-0612-2693 Cid Colom, Jordi|||0000-0002-6406-0585 Lozano, Miquel|||0000-0003-2593-833X García, E. Tabera, Jaime|||0000-0002-5430-0151 Trias, E. Perpiña, U. Canals, Josep M.|||0000-0001-6829-7670 Baumann, Tycho|||0000-0003-4421-0088 Benítez Ribas, Daniel|||0000-0002-2346-5324 Campo, Elias|||0000-0001-9850-9793 Yagüe, Jordi|||0000-0001-8210-1929 Urbano Ispizua, Álvaro|||0000-0002-7529-9399 Rives, S. Delgado, Julio|||0000-0002-5157-4376 Juan, Manel|||0000-0002-3064-1648 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Chimeric antigen receptor CD19 Leukemia Lymphoma Immunotherapy CAR T-cell production CliniMACS Prodigy |
| topic |
Chimeric antigen receptor CD19 Leukemia Lymphoma Immunotherapy CAR T-cell production CliniMACS Prodigy |
| description |
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. T and T were the predominant T-cell phenotypes obtained. 38.7% of CAR T-cells obtained presented a TN or T 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 T, T, and T cells, while T 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. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2 2020-01-01 2020 2020-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/236426 https://dx.doi.org/urn:doi:10.3389/fimmu.2020.00482 |
| url |
https://ddd.uab.cat/record/236426 https://dx.doi.org/urn:doi:10.3389/fimmu.2020.00482 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI13-00676 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIE13-00033 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-01043 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PICIS14-00122 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18-00775 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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1869416912473030656 |
| spelling |
Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactorExperience from an academic phase i clinical trialCastellà, MariaCaballero-Baños, M.Ortiz-Maldonado, Valentín|||0000-0003-4699-6862González-Navarro, Europa Azucena|||0000-0003-3310-5557Suñé, Guillermo|||0000-0002-4034-4348Antoñana Vildosola, Asier|||0000-0002-1404-6398Boronat Barado, AnnaMarzal, BertaMillán, LucíaMartín-Antonio, B.|||0000-0003-0612-2693Cid Colom, Jordi|||0000-0002-6406-0585Lozano, Miquel|||0000-0003-2593-833XGarcía, E.Tabera, Jaime|||0000-0002-5430-0151Trias, E.Perpiña, U.Canals, Josep M.|||0000-0001-6829-7670Baumann, Tycho|||0000-0003-4421-0088Benítez Ribas, Daniel|||0000-0002-2346-5324Campo, Elias|||0000-0001-9850-9793Yagüe, Jordi|||0000-0001-8210-1929Urbano Ispizua, Álvaro|||0000-0002-7529-9399Rives, S.Delgado, Julio|||0000-0002-5157-4376Juan, Manel|||0000-0002-3064-1648Chimeric antigen receptorCD19LeukemiaLymphomaImmunotherapyCAR T-cell productionCliniMACS ProdigyDevelopment 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. T and T were the predominant T-cell phenotypes obtained. 38.7% of CAR T-cells obtained presented a TN or T 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 T, T, and T cells, while T 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.Universitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/236426https://dx.doi.org/urn:doi:10.3389/fimmu.2020.00482reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI13-00676Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIE13-00033Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-01043Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PICIS14-00122Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18-00775open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2364262026-06-06T12:50:31Z |
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15,300719 |