Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions

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...

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Autores: Castellà Castellà, Maria, Boronat, Anna, Martín Ibáñez, Raquel, Rodríguez, Vanina, Suñé, Guillermo, Caballero, Miguel, Marzal Martí, Berta, Pérez-Amill, Lorena, Martín-Antonio, Beatriz, Castaño, Julio, Bueno, Clara, Balagué, Olga, González Navarro, E. Azucena, Serra Pagès, Carles, Engel Rocamora, Pablo, Vilella, Ramon, Benítez-Ribas, Daniel, Ortiz-Maldonado Gibson, Valentín, Cid Vidal, Joan, Tabera, Jaime, Canals i Coll, Josep M., Lozano, Miquel, Baumann, Tycho, Vilarrodona, Anna, Trias, Esteve, Campo Güerri, Elias, Menéndez Buján, Pablo, Urbano Ispizua, Álvaro, Yagüe, Jordi, Pérez Galán, Patricia, Rives Solà, Susana, Delgado, Julio (Delgado González), Juan, Manel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/147807
Acceso en línea:https://hdl.handle.net/2445/147807
Access Level:acceso abierto
Palabra clave:Immunoteràpia
Leucèmia
Limfomes
Cèl·lules T
Immunotheraphy
Leukemia
Lymphomas
T cells
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repository_id_str
spelling Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutionsCastellà Castellà, MariaBoronat, AnnaMartín Ibáñez, RaquelRodríguez, VaninaSuñé, GuillermoCaballero, MiguelMarzal Martí, BertaPérez-Amill, LorenaMartín-Antonio, BeatrizCastaño, JulioBueno, ClaraBalagué, OlgaGonzález Navarro, E. AzucenaSerra Pagès, CarlesEngel Rocamora, PabloVilella, RamonBenítez-Ribas, DanielOrtiz-Maldonado Gibson, ValentínCid Vidal, JoanTabera, JaimeCanals i Coll, Josep M.Lozano, MiquelBaumann, TychoVilarrodona, AnnaTrias, EsteveCampo Güerri, EliasMenéndez Buján, PabloUrbano Ispizua, ÁlvaroYagüe, JordiPérez Galán, PatriciaRives Solà, SusanaDelgado, Julio (Delgado González)Juan, ManelImmunoteràpiaLeucèmiaLimfomesCèl·lules TImmunotheraphyLeukemiaLymphomasT cellsGenetically 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-Prkdcscid Il2rdtm1Wjl/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.Cell Press2020202020182020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/147807Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.omtm.2018.11.010Molecular Therapy-Methods & Clinical Development, 2018, vol. 12, p. 134-144https://doi.org/10.1016/j.omtm.2018.11.010info:eu-repo/grantAgreement/EC/H2020/646903info:eu-repo/grantAgreement/EC/H2020/811220cc-by (c) Castella, Maria et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1478072026-05-29T05:05:01Z
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: A paradigm for an affordable CAR T cell production at academic institutions
spellingShingle Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions
Castellà Castellà, Maria
Immunoteràpia
Leucèmia
Limfomes
Cèl·lules T
Immunotheraphy
Leukemia
Lymphomas
T cells
title_short Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions
title_full Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions
title_fullStr Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions
title_full_unstemmed Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions
title_sort Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions
dc.creator.none.fl_str_mv Castellà Castellà, Maria
Boronat, Anna
Martín Ibáñez, Raquel
Rodríguez, Vanina
Suñé, Guillermo
Caballero, Miguel
Marzal Martí, Berta
Pérez-Amill, Lorena
Martín-Antonio, Beatriz
Castaño, Julio
Bueno, Clara
Balagué, Olga
González Navarro, E. Azucena
Serra Pagès, Carles
Engel Rocamora, Pablo
Vilella, Ramon
Benítez-Ribas, Daniel
Ortiz-Maldonado Gibson, Valentín
Cid Vidal, Joan
Tabera, Jaime
Canals i Coll, Josep M.
Lozano, Miquel
Baumann, Tycho
Vilarrodona, Anna
Trias, Esteve
Campo Güerri, Elias
Menéndez Buján, Pablo
Urbano Ispizua, Álvaro
Yagüe, Jordi
Pérez Galán, Patricia
Rives Solà, Susana
Delgado, Julio (Delgado González)
Juan, Manel
author Castellà Castellà, Maria
author_facet Castellà Castellà, Maria
Boronat, Anna
Martín Ibáñez, Raquel
Rodríguez, Vanina
Suñé, Guillermo
Caballero, Miguel
Marzal Martí, Berta
Pérez-Amill, Lorena
Martín-Antonio, Beatriz
Castaño, Julio
Bueno, Clara
Balagué, Olga
González Navarro, E. Azucena
Serra Pagès, Carles
Engel Rocamora, Pablo
Vilella, Ramon
Benítez-Ribas, Daniel
Ortiz-Maldonado Gibson, Valentín
Cid Vidal, Joan
Tabera, Jaime
Canals i Coll, Josep M.
Lozano, Miquel
Baumann, Tycho
Vilarrodona, Anna
Trias, Esteve
Campo Güerri, Elias
Menéndez Buján, Pablo
Urbano Ispizua, Álvaro
Yagüe, Jordi
Pérez Galán, Patricia
Rives Solà, Susana
Delgado, Julio (Delgado González)
Juan, Manel
author_role author
author2 Boronat, Anna
Martín Ibáñez, Raquel
Rodríguez, Vanina
Suñé, Guillermo
Caballero, Miguel
Marzal Martí, Berta
Pérez-Amill, Lorena
Martín-Antonio, Beatriz
Castaño, Julio
Bueno, Clara
Balagué, Olga
González Navarro, E. Azucena
Serra Pagès, Carles
Engel Rocamora, Pablo
Vilella, Ramon
Benítez-Ribas, Daniel
Ortiz-Maldonado Gibson, Valentín
Cid Vidal, Joan
Tabera, Jaime
Canals i Coll, Josep M.
Lozano, Miquel
Baumann, Tycho
Vilarrodona, Anna
Trias, Esteve
Campo Güerri, Elias
Menéndez Buján, Pablo
Urbano Ispizua, Álvaro
Yagüe, Jordi
Pérez Galán, Patricia
Rives Solà, Susana
Delgado, Julio (Delgado González)
Juan, Manel
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.subject.none.fl_str_mv Immunoteràpia
Leucèmia
Limfomes
Cèl·lules T
Immunotheraphy
Leukemia
Lymphomas
T cells
topic Immunoteràpia
Leucèmia
Limfomes
Cèl·lules T
Immunotheraphy
Leukemia
Lymphomas
T cells
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-Prkdcscid Il2rdtm1Wjl/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 2018
dc.date.none.fl_str_mv 2018
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/147807
url https://hdl.handle.net/2445/147807
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.omtm.2018.11.010
Molecular Therapy-Methods & Clinical Development, 2018, vol. 12, p. 134-144
https://doi.org/10.1016/j.omtm.2018.11.010
info:eu-repo/grantAgreement/EC/H2020/646903
info:eu-repo/grantAgreement/EC/H2020/811220
dc.rights.none.fl_str_mv cc-by (c) Castella, Maria et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Castella, Maria et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414932275003392
score 15.812429

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