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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2018 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/147807 |
| Online Access: | https://hdl.handle.net/2445/147807 |
| Access Level: | Open access |
| Keyword: | Immunoteràpia Leucèmia Limfomes Cèl·lules T Immunotheraphy Leukemia Lymphomas T cells |
| _version_ | 1878737419548753920 |
|---|---|
| author | Castellà Castellà, Maria |
| 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 |
| author_browse | Balagué, Olga Baumann, Tycho Benítez-Ribas, Daniel Boronat, Anna Bueno, Clara Caballero, Miguel Campo Güerri, Elias Canals i Coll, Josep M. Castaño, Julio Castellà Castellà, Maria Cid Vidal, Joan Delgado, Julio (Delgado González) Engel Rocamora, Pablo González Navarro, E. Azucena Juan, Manel Lozano, Miquel Martín Ibáñez, Raquel Martín-Antonio, Beatriz Marzal Martí, Berta Menéndez Buján, Pablo Ortiz-Maldonado Gibson, Valentín Pérez Galán, Patricia Pérez-Amill, Lorena Rives Solà, Susana Rodríguez, Vanina Serra Pagès, Carles Suñé, Guillermo Tabera, Jaime Trias, Esteve Urbano Ispizua, Álvaro Vilarrodona, Anna Vilella, Ramon Yagüe, Jordi |
| 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 |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_9f7c368a67bb2db4ee67514cb63bcdcf |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:2445/147807 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | Cell Press |
| publisherStr | Cell Press |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions 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 Immunoteràpia Leucèmia Limfomes Cèl·lules T Immunotheraphy Leukemia Lymphomas T cells 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. Cell Press https://hdl.handle.net/2445/147807 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Immunoteràpia Leucèmia Limfomes Cèl·lules T Immunotheraphy Leukemia Lymphomas T cells |
| topic_facet | Immunoteràpia Leucèmia Limfomes Cèl·lules T Immunotheraphy Leukemia Lymphomas T cells |
| url | https://hdl.handle.net/2445/147807 |