Development of a Novel Anti-CD19 Chimeric Antigen Receptor
Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:285231 |
| Acceso en línea: | https://ddd.uab.cat/record/285231 https://dx.doi.org/urn:doi:10.1016/j.omtm.2018.11.010 |
| Access Level: | acceso abierto |
| Palabra clave: | 4-1BB CD19 T cell Chimeric antigen receptor Immunotherapy Leukemia Lymphoma Preclinical studies |
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Development of a Novel Anti-CD19 Chimeric Antigen ReceptorA Paradigm for an Affordable CAR T Cell Production at Academic InstitutionsCastellà, MariaBoronat, Anna|||0000-0003-0852-3634Martín-Ibáñez, RaquelRodríguez, VaninaSuñé, Guillermo|||0000-0002-4034-4348Caballero, Miguel|||0000-0002-2313-7988Marzal, BertaPérez-Amill, Lorena|||0000-0003-0674-4660Martín-Antonio, B.|||0000-0003-0612-2693Castaño Cardoso, Julio|||0000-0002-0712-5856Bueno, Clara|||0000-0003-1442-6216Balagué, Olga|||0000-0002-5099-3675González-Navarro, Europa Azucena|||0000-0003-3310-5557Serra-Pages, CarlesEngel, Pablo|||0000-0001-8410-252XVilella, RamonBenítez Ribas, Daniel|||0000-0002-2346-5324Ortiz-Maldonado, Valentín|||0000-0003-4699-6862Cid, Joan|||0000-0001-5445-4508Tabera, Jaime|||0000-0002-5430-0151Canals, Josep M.|||0000-0001-6829-7670Lozano, Miquel|||0000-0003-2593-833XBaumann, Tycho|||0000-0003-4421-0088Vilarrodona, Ana|||0000-0001-6984-1834Trias, Esteve|||0000-0001-7635-4428Campo, Elias|||0000-0001-9850-9793Menéndez Bujan, Pablo|||0000-0001-9372-1007Urbano Ispizua, Álvaro|||0000-0002-7529-9399Yagüe, Jordi|||0000-0001-8210-1929Pérez-Galán, Patricia|||0000-0003-3895-5024Rives, Susana|||0000-0002-5658-1831Delgado, Julio|||0000-0002-5157-4376Juan, Manel|||0000-0002-3064-16484-1BBCD19T cellChimeric antigen receptorImmunotherapyLeukemiaLymphomaPreclinical studiesGenetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdc Il2rd/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients.Universitat Autònoma de Barcelona 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/285231https://dx.doi.org/urn:doi:10.1016/j.omtm.2018.11.010reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00676Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE13/00033Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/01043Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/01028open 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:2852312026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor A Paradigm for an Affordable CAR T Cell Production at Academic Institutions |
| title |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor |
| spellingShingle |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor Castellà, Maria 4-1BB CD19 T cell Chimeric antigen receptor Immunotherapy Leukemia Lymphoma Preclinical studies |
| title_short |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor |
| title_full |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor |
| title_fullStr |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor |
| title_full_unstemmed |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor |
| title_sort |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor |
| dc.creator.none.fl_str_mv |
Castellà, Maria Boronat, Anna|||0000-0003-0852-3634 Martín-Ibáñez, Raquel Rodríguez, Vanina Suñé, Guillermo|||0000-0002-4034-4348 Caballero, Miguel|||0000-0002-2313-7988 Marzal, Berta Pérez-Amill, Lorena|||0000-0003-0674-4660 Martín-Antonio, B.|||0000-0003-0612-2693 Castaño Cardoso, Julio|||0000-0002-0712-5856 Bueno, Clara|||0000-0003-1442-6216 Balagué, Olga|||0000-0002-5099-3675 González-Navarro, Europa Azucena|||0000-0003-3310-5557 Serra-Pages, Carles Engel, Pablo|||0000-0001-8410-252X Vilella, Ramon Benítez Ribas, Daniel|||0000-0002-2346-5324 Ortiz-Maldonado, Valentín|||0000-0003-4699-6862 Cid, Joan|||0000-0001-5445-4508 Tabera, Jaime|||0000-0002-5430-0151 Canals, Josep M.|||0000-0001-6829-7670 Lozano, Miquel|||0000-0003-2593-833X Baumann, Tycho|||0000-0003-4421-0088 Vilarrodona, Ana|||0000-0001-6984-1834 Trias, Esteve|||0000-0001-7635-4428 Campo, Elias|||0000-0001-9850-9793 Menéndez Bujan, Pablo|||0000-0001-9372-1007 Urbano Ispizua, Álvaro|||0000-0002-7529-9399 Yagüe, Jordi|||0000-0001-8210-1929 Pérez-Galán, Patricia|||0000-0003-3895-5024 Rives, Susana|||0000-0002-5658-1831 Delgado, Julio|||0000-0002-5157-4376 Juan, Manel|||0000-0002-3064-1648 |
| author |
Castellà, Maria |
| author_facet |
Castellà, Maria Boronat, Anna|||0000-0003-0852-3634 Martín-Ibáñez, Raquel Rodríguez, Vanina Suñé, Guillermo|||0000-0002-4034-4348 Caballero, Miguel|||0000-0002-2313-7988 Marzal, Berta Pérez-Amill, Lorena|||0000-0003-0674-4660 Martín-Antonio, B.|||0000-0003-0612-2693 Castaño Cardoso, Julio|||0000-0002-0712-5856 Bueno, Clara|||0000-0003-1442-6216 Balagué, Olga|||0000-0002-5099-3675 González-Navarro, Europa Azucena|||0000-0003-3310-5557 Serra-Pages, Carles Engel, Pablo|||0000-0001-8410-252X Vilella, Ramon Benítez Ribas, Daniel|||0000-0002-2346-5324 Ortiz-Maldonado, Valentín|||0000-0003-4699-6862 Cid, Joan|||0000-0001-5445-4508 Tabera, Jaime|||0000-0002-5430-0151 Canals, Josep M.|||0000-0001-6829-7670 Lozano, Miquel|||0000-0003-2593-833X Baumann, Tycho|||0000-0003-4421-0088 Vilarrodona, Ana|||0000-0001-6984-1834 Trias, Esteve|||0000-0001-7635-4428 Campo, Elias|||0000-0001-9850-9793 Menéndez Bujan, Pablo|||0000-0001-9372-1007 Urbano Ispizua, Álvaro|||0000-0002-7529-9399 Yagüe, Jordi|||0000-0001-8210-1929 Pérez-Galán, Patricia|||0000-0003-3895-5024 Rives, Susana|||0000-0002-5658-1831 Delgado, Julio|||0000-0002-5157-4376 Juan, Manel|||0000-0002-3064-1648 |
| author_role |
author |
| author2 |
Boronat, Anna|||0000-0003-0852-3634 Martín-Ibáñez, Raquel Rodríguez, Vanina Suñé, Guillermo|||0000-0002-4034-4348 Caballero, Miguel|||0000-0002-2313-7988 Marzal, Berta Pérez-Amill, Lorena|||0000-0003-0674-4660 Martín-Antonio, B.|||0000-0003-0612-2693 Castaño Cardoso, Julio|||0000-0002-0712-5856 Bueno, Clara|||0000-0003-1442-6216 Balagué, Olga|||0000-0002-5099-3675 González-Navarro, Europa Azucena|||0000-0003-3310-5557 Serra-Pages, Carles Engel, Pablo|||0000-0001-8410-252X Vilella, Ramon Benítez Ribas, Daniel|||0000-0002-2346-5324 Ortiz-Maldonado, Valentín|||0000-0003-4699-6862 Cid, Joan|||0000-0001-5445-4508 Tabera, Jaime|||0000-0002-5430-0151 Canals, Josep M.|||0000-0001-6829-7670 Lozano, Miquel|||0000-0003-2593-833X Baumann, Tycho|||0000-0003-4421-0088 Vilarrodona, Ana|||0000-0001-6984-1834 Trias, Esteve|||0000-0001-7635-4428 Campo, Elias|||0000-0001-9850-9793 Menéndez Bujan, Pablo|||0000-0001-9372-1007 Urbano Ispizua, Álvaro|||0000-0002-7529-9399 Yagüe, Jordi|||0000-0001-8210-1929 Pérez-Galán, Patricia|||0000-0003-3895-5024 Rives, Susana|||0000-0002-5658-1831 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 author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
4-1BB CD19 T cell Chimeric antigen receptor Immunotherapy Leukemia Lymphoma Preclinical studies |
| topic |
4-1BB CD19 T cell Chimeric antigen receptor Immunotherapy Leukemia Lymphoma Preclinical studies |
| description |
Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdc Il2rd/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2 2019-01-01 2019 2019-01-01 |
| 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/285231 https://dx.doi.org/urn:doi:10.1016/j.omtm.2018.11.010 |
| url |
https://ddd.uab.cat/record/285231 https://dx.doi.org/urn:doi:10.1016/j.omtm.2018.11.010 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00676 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 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 PI17/01028 |
| 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/ |
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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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Dipòsit Digital de Documents de la UAB |
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