Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/147807
Title: Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions
Author: 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, Pablo
Urbano Ispizua, Álvaro
Yagüe, Jordi
Pérez Galán, Patricia
Rives, Susana
Delgado, Julio (Delgado González)
Juan, Manel
Keywords: Immunoteràpia
Leucèmia
Limfomes
Cèl·lules T
Immunotheraphy
Leukemia
Lymphomas
T cells
Issue Date: 6-Dec-2018
Publisher: Cell Press
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.
Note: Reproducció del document publicat a: https://doi.org/10.1016/j.omtm.2018.11.010
It is part of: Molecular Therapy-Methods & Clinical Development, 2018, vol. 12, p. 134-144
URI: http://hdl.handle.net/2445/147807
Related resource: https://doi.org/10.1016/j.omtm.2018.11.010
ISSN: 2329-0501
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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