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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
Menendez, Pablo
Urbano Ispizua, Álvaro
Yagüe, Jordi
Pérez Galán, Patricia
Rives, Susana
Delgado, Julio
Juan, Manel
Keywords: Immunoteràpia
Cèl·lules T
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.
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It is part of: Molecular Therapy-Methods & Clinical Development, 2018, vol. 12, p. 134-144
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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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