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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 Martí, 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 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, 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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