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

• Published in: Molecular therapy. Methods & clinical development Vol. 12; pp. 134 - 144
• Main Authors: 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-Pages, Carles, Engel, Pablo, Vilella, Ramon, Benitez-Ribas, Daniel, Ortiz-Maldonado, Valentín, Cid, Joan, Tabera, Jaime, Canals, Josep M, Lozano, Miquel, Baumann, Tycho, Vilarrodona, Anna, Trias, Esteve, Campo, Elías, Menendez, Pablo, Urbano-Ispizua, Álvaro, Yagüe, Jordi, Pérez-Galán, Patricia, Rives, Susana, Delgado, Julio, Juan, Manel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 15.03.2019; Cell Press; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Antigens; Cancer; CD19 antigen; CD8 antigen; Cell growth; Cell proliferation; Chimeric antigen receptors; Clinical trials; Cytotoxicity; Cèl·lules T; Flow cytometry; Immunoteràpia; Immunotheraphy; Inflammation; Leucèmia; Leukemia; Limfomes; Lymphocytes; Lymphocytes T; Lymphoma; Lymphomas; Medical research; Patients; T cells; United States > US; leukemia; preclinical studies; CD19; T cell; immunotherapy; lymphoma; 4-1BB; chimeric antigen receptor
• ISSN: 2329-0501; 2329-0501
• DOI: 10.1016/j.omtm.2018.11.010

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 , inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. , A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg- /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.