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Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions

2018; Cell Press; Volume: 12; Linguagem: Inglês

10.1016/j.omtm.2018.11.010

2329-0501

María Castellá, Anna Boronat, Raquel Martín‐Ibáñez, Vanina Rodríguez, Guillermo Suñé, Miguel Caballero‐Baños, Berta Marzal, Lorena Pérez-Amill, Beatriz Martín-Antonio, Julio Castaño, Clara Bueno, Olga Balagué, Azucena González-Navarro, Carles Serra‐Pages, Pablo Engel, R. Vilella, Daniel Benítez‐Ribas, Valentín Ortiz‐Maldonado, Joan Cid, Jaime Tabera, Josep M. Canals, Miquel Lozano, Tycho Baumann, Anna Vilarrodona, Esteve Trias, Elı́as Campo, Pablo Menéndez, Álvaro Urbano‐Ispizua, Jordi Yagüe, Patricia Pérez‐Galán, Susana Rives, Julio Delgado, Manel Juan,

Nanowire Synthesis and Applications

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-PrkdcscidIl2rdtm1Wjl /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.