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...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Maria Castella [verfasserIn] Anna Boronat [verfasserIn] Raquel Martín-Ibáñez [verfasserIn] Vanina Rodríguez [verfasserIn] Guillermo Suñé [verfasserIn] Miguel Caballero [verfasserIn] Berta Marzal [verfasserIn] Lorena Pérez-Amill [verfasserIn] Beatriz Martín-Antonio [verfasserIn] Julio Castaño [verfasserIn] Clara Bueno [verfasserIn] Olga Balagué [verfasserIn] Europa Azucena González-Navarro [verfasserIn] Carles Serra-Pages [verfasserIn] Pablo Engel [verfasserIn] Ramon Vilella [verfasserIn] Daniel Benitez-Ribas [verfasserIn] Valentín Ortiz-Maldonado [verfasserIn] Joan Cid [verfasserIn] Jaime Tabera [verfasserIn] Josep M. Canals [verfasserIn] Miquel Lozano [verfasserIn] Tycho Baumann [verfasserIn] Anna Vilarrodona [verfasserIn] Esteve Trias [verfasserIn] Elías Campo [verfasserIn] Pablo Menendez [verfasserIn] Álvaro Urbano-Ispizua [verfasserIn] Jordi Yagüe [verfasserIn] Patricia Pérez-Galán [verfasserIn] Susana Rives [verfasserIn] Julio Delgado [verfasserIn] Manel Juan [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019 |
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| Übergeordnetes Werk: |
In: Molecular Therapy: Methods & Clinical Development - Elsevier, 2015, 12(2019), Seite 134-144 |
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| Übergeordnetes Werk: |
volume:12 ; year:2019 ; pages:134-144 |
| Links: |
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| DOI / URN: |
10.1016/j.omtm.2018.11.010 |
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| Katalog-ID: |
DOAJ063916231 |
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| 520 | |a 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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies | ||
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10.1016/j.omtm.2018.11.010 doi (DE-627)DOAJ063916231 (DE-599)DOAJ0991d78034c649d5800886f6bf312afe DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Maria Castella verfasserin aut Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies Genetics Cytology Anna Boronat verfasserin aut Raquel Martín-Ibáñez verfasserin aut Vanina Rodríguez verfasserin aut Guillermo Suñé verfasserin aut Miguel Caballero verfasserin aut Berta Marzal verfasserin aut Lorena Pérez-Amill verfasserin aut Beatriz Martín-Antonio verfasserin aut Julio Castaño verfasserin aut Clara Bueno verfasserin aut Olga Balagué verfasserin aut Europa Azucena González-Navarro verfasserin aut Carles Serra-Pages verfasserin aut Pablo Engel verfasserin aut Ramon Vilella verfasserin aut Daniel Benitez-Ribas verfasserin aut Valentín Ortiz-Maldonado verfasserin aut Joan Cid verfasserin aut Jaime Tabera verfasserin aut Josep M. Canals verfasserin aut Miquel Lozano verfasserin aut Tycho Baumann verfasserin aut Anna Vilarrodona verfasserin aut Esteve Trias verfasserin aut Elías Campo verfasserin aut Pablo Menendez verfasserin aut Álvaro Urbano-Ispizua verfasserin aut Jordi Yagüe verfasserin aut Patricia Pérez-Galán verfasserin aut Susana Rives verfasserin aut Julio Delgado verfasserin aut Manel Juan verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 12(2019), Seite 134-144 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:12 year:2019 pages:134-144 https://doi.org/10.1016/j.omtm.2018.11.010 kostenfrei https://doaj.org/article/0991d78034c649d5800886f6bf312afe kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050118301220 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2019 134-144 |
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10.1016/j.omtm.2018.11.010 doi (DE-627)DOAJ063916231 (DE-599)DOAJ0991d78034c649d5800886f6bf312afe DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Maria Castella verfasserin aut Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies Genetics Cytology Anna Boronat verfasserin aut Raquel Martín-Ibáñez verfasserin aut Vanina Rodríguez verfasserin aut Guillermo Suñé verfasserin aut Miguel Caballero verfasserin aut Berta Marzal verfasserin aut Lorena Pérez-Amill verfasserin aut Beatriz Martín-Antonio verfasserin aut Julio Castaño verfasserin aut Clara Bueno verfasserin aut Olga Balagué verfasserin aut Europa Azucena González-Navarro verfasserin aut Carles Serra-Pages verfasserin aut Pablo Engel verfasserin aut Ramon Vilella verfasserin aut Daniel Benitez-Ribas verfasserin aut Valentín Ortiz-Maldonado verfasserin aut Joan Cid verfasserin aut Jaime Tabera verfasserin aut Josep M. Canals verfasserin aut Miquel Lozano verfasserin aut Tycho Baumann verfasserin aut Anna Vilarrodona verfasserin aut Esteve Trias verfasserin aut Elías Campo verfasserin aut Pablo Menendez verfasserin aut Álvaro Urbano-Ispizua verfasserin aut Jordi Yagüe verfasserin aut Patricia Pérez-Galán verfasserin aut Susana Rives verfasserin aut Julio Delgado verfasserin aut Manel Juan verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 12(2019), Seite 134-144 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:12 year:2019 pages:134-144 https://doi.org/10.1016/j.omtm.2018.11.010 kostenfrei https://doaj.org/article/0991d78034c649d5800886f6bf312afe kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050118301220 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2019 134-144 |
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10.1016/j.omtm.2018.11.010 doi (DE-627)DOAJ063916231 (DE-599)DOAJ0991d78034c649d5800886f6bf312afe DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Maria Castella verfasserin aut Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies Genetics Cytology Anna Boronat verfasserin aut Raquel Martín-Ibáñez verfasserin aut Vanina Rodríguez verfasserin aut Guillermo Suñé verfasserin aut Miguel Caballero verfasserin aut Berta Marzal verfasserin aut Lorena Pérez-Amill verfasserin aut Beatriz Martín-Antonio verfasserin aut Julio Castaño verfasserin aut Clara Bueno verfasserin aut Olga Balagué verfasserin aut Europa Azucena González-Navarro verfasserin aut Carles Serra-Pages verfasserin aut Pablo Engel verfasserin aut Ramon Vilella verfasserin aut Daniel Benitez-Ribas verfasserin aut Valentín Ortiz-Maldonado verfasserin aut Joan Cid verfasserin aut Jaime Tabera verfasserin aut Josep M. Canals verfasserin aut Miquel Lozano verfasserin aut Tycho Baumann verfasserin aut Anna Vilarrodona verfasserin aut Esteve Trias verfasserin aut Elías Campo verfasserin aut Pablo Menendez verfasserin aut Álvaro Urbano-Ispizua verfasserin aut Jordi Yagüe verfasserin aut Patricia Pérez-Galán verfasserin aut Susana Rives verfasserin aut Julio Delgado verfasserin aut Manel Juan verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 12(2019), Seite 134-144 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:12 year:2019 pages:134-144 https://doi.org/10.1016/j.omtm.2018.11.010 kostenfrei https://doaj.org/article/0991d78034c649d5800886f6bf312afe kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050118301220 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2019 134-144 |
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10.1016/j.omtm.2018.11.010 doi (DE-627)DOAJ063916231 (DE-599)DOAJ0991d78034c649d5800886f6bf312afe DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Maria Castella verfasserin aut Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies Genetics Cytology Anna Boronat verfasserin aut Raquel Martín-Ibáñez verfasserin aut Vanina Rodríguez verfasserin aut Guillermo Suñé verfasserin aut Miguel Caballero verfasserin aut Berta Marzal verfasserin aut Lorena Pérez-Amill verfasserin aut Beatriz Martín-Antonio verfasserin aut Julio Castaño verfasserin aut Clara Bueno verfasserin aut Olga Balagué verfasserin aut Europa Azucena González-Navarro verfasserin aut Carles Serra-Pages verfasserin aut Pablo Engel verfasserin aut Ramon Vilella verfasserin aut Daniel Benitez-Ribas verfasserin aut Valentín Ortiz-Maldonado verfasserin aut Joan Cid verfasserin aut Jaime Tabera verfasserin aut Josep M. Canals verfasserin aut Miquel Lozano verfasserin aut Tycho Baumann verfasserin aut Anna Vilarrodona verfasserin aut Esteve Trias verfasserin aut Elías Campo verfasserin aut Pablo Menendez verfasserin aut Álvaro Urbano-Ispizua verfasserin aut Jordi Yagüe verfasserin aut Patricia Pérez-Galán verfasserin aut Susana Rives verfasserin aut Julio Delgado verfasserin aut Manel Juan verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 12(2019), Seite 134-144 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:12 year:2019 pages:134-144 https://doi.org/10.1016/j.omtm.2018.11.010 kostenfrei https://doaj.org/article/0991d78034c649d5800886f6bf312afe kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050118301220 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2019 134-144 |
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10.1016/j.omtm.2018.11.010 doi (DE-627)DOAJ063916231 (DE-599)DOAJ0991d78034c649d5800886f6bf312afe DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Maria Castella verfasserin aut Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies Genetics Cytology Anna Boronat verfasserin aut Raquel Martín-Ibáñez verfasserin aut Vanina Rodríguez verfasserin aut Guillermo Suñé verfasserin aut Miguel Caballero verfasserin aut Berta Marzal verfasserin aut Lorena Pérez-Amill verfasserin aut Beatriz Martín-Antonio verfasserin aut Julio Castaño verfasserin aut Clara Bueno verfasserin aut Olga Balagué verfasserin aut Europa Azucena González-Navarro verfasserin aut Carles Serra-Pages verfasserin aut Pablo Engel verfasserin aut Ramon Vilella verfasserin aut Daniel Benitez-Ribas verfasserin aut Valentín Ortiz-Maldonado verfasserin aut Joan Cid verfasserin aut Jaime Tabera verfasserin aut Josep M. Canals verfasserin aut Miquel Lozano verfasserin aut Tycho Baumann verfasserin aut Anna Vilarrodona verfasserin aut Esteve Trias verfasserin aut Elías Campo verfasserin aut Pablo Menendez verfasserin aut Álvaro Urbano-Ispizua verfasserin aut Jordi Yagüe verfasserin aut Patricia Pérez-Galán verfasserin aut Susana Rives verfasserin aut Julio Delgado verfasserin aut Manel Juan verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 12(2019), Seite 134-144 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:12 year:2019 pages:134-144 https://doi.org/10.1016/j.omtm.2018.11.010 kostenfrei https://doaj.org/article/0991d78034c649d5800886f6bf312afe kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050118301220 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2019 134-144 |
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Maria Castella @@aut@@ Anna Boronat @@aut@@ Raquel Martín-Ibáñez @@aut@@ Vanina Rodríguez @@aut@@ Guillermo Suñé @@aut@@ Miguel Caballero @@aut@@ Berta Marzal @@aut@@ Lorena Pérez-Amill @@aut@@ Beatriz Martín-Antonio @@aut@@ Julio Castaño @@aut@@ Clara Bueno @@aut@@ Olga Balagué @@aut@@ Europa Azucena González-Navarro @@aut@@ Carles Serra-Pages @@aut@@ Pablo Engel @@aut@@ Ramon Vilella @@aut@@ Daniel Benitez-Ribas @@aut@@ Valentín Ortiz-Maldonado @@aut@@ Joan Cid @@aut@@ Jaime Tabera @@aut@@ Josep M. Canals @@aut@@ Miquel Lozano @@aut@@ Tycho Baumann @@aut@@ Anna Vilarrodona @@aut@@ Esteve Trias @@aut@@ Elías Campo @@aut@@ Pablo Menendez @@aut@@ Álvaro Urbano-Ispizua @@aut@@ Jordi Yagüe @@aut@@ Patricia Pérez-Galán @@aut@@ Susana Rives @@aut@@ Julio Delgado @@aut@@ Manel Juan @@aut@@ |
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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. 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development of a novel anti-cd19 chimeric antigen receptor: a paradigm for an affordable car t cell production at academic institutions |
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Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions |
| abstract |
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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies |
| abstractGer |
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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies |
| abstract_unstemmed |
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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies |
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| title_short |
Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions |
| url |
https://doi.org/10.1016/j.omtm.2018.11.010 https://doaj.org/article/0991d78034c649d5800886f6bf312afe http://www.sciencedirect.com/science/article/pii/S2329050118301220 https://doaj.org/toc/2329-0501 |
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Anna Boronat Raquel Martín-Ibáñez Vanina Rodríguez Guillermo Suñé Miguel Caballero Berta Marzal Lorena Pérez-Amill Beatriz Martín-Antonio Julio Castaño Clara Bueno Olga Balagué Europa Azucena González-Navarro Carles Serra-Pages Pablo Engel Ramon Vilella Daniel Benitez-Ribas Valentín Ortiz-Maldonado Joan Cid Jaime Tabera Josep M. Canals Miquel Lozano Tycho Baumann Anna Vilarrodona Esteve Trias Elías Campo Pablo Menendez Álvaro Urbano-Ispizua Jordi Yagüe Patricia Pérez-Galán Susana Rives Julio Delgado Manel Juan |
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Anna Boronat Raquel Martín-Ibáñez Vanina Rodríguez Guillermo Suñé Miguel Caballero Berta Marzal Lorena Pérez-Amill Beatriz Martín-Antonio Julio Castaño Clara Bueno Olga Balagué Europa Azucena González-Navarro Carles Serra-Pages Pablo Engel Ramon Vilella Daniel Benitez-Ribas Valentín Ortiz-Maldonado Joan Cid Jaime Tabera Josep M. Canals Miquel Lozano Tycho Baumann Anna Vilarrodona Esteve Trias Elías Campo Pablo Menendez Álvaro Urbano-Ispizua Jordi Yagüe Patricia Pérez-Galán Susana Rives Julio Delgado Manel Juan |
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QH - Natural History and Biology |
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10.1016/j.omtm.2018.11.010 |
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2024-07-03T20:13:48.803Z |
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|
| score |
7.402523 |