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Título:	Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions
Autor/a:	Castella, Maria; Boronat, Anna; Martín Ibáñez, Raquel; Rodríguez, Vanina; Suñé, Guillermo; Caballero, Miguel; Marzal, Berta; Pérez-Amill, Lorena; Martín-Antonio, Beatriz; Castaño, Julio; Bueno, Clara; Balagué, Olga; González-Navarro, Europa Azucena; Serra Pagès, Carles; Engel Rocamora, Pablo; Vilella, Ramon; Benítez-Ribas, Daniel; Ortiz-Maldonado, 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, Susana; Delgado, Julio (Delgado González); Juan, Manel
Notas:	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.
Materia(s):	-Immunoteràpia -Leucèmia -Limfomes -Cèl·lules T -Immunotheraphy -Leukemia -Lymphomas -T cells
Derechos:	cc-by (c) Castella, Maria et al., 2018 http://creativecommons.org/licenses/by/3.0/es
Tipo de documento:	Artículo Artículo - Versión publicada
Editor:	Cell Press
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