| Autor: |
Maria Castella, Anna Boronat, Raquel Martín-Ibáñez, Vanina Rodríguez, Guillermo Suñé, Miguel Caballero, Berta Marzal, Lorena Pérez-Amill, Beatriz Martín-Antonio, Julio Castaño, Clara Bueno, Olga Balagué, Europa Azucena González-Navarro, Carles Serra-Pages, Pablo Engel, Ramon Vilella, Daniel Benitez-Ribas, Valentín Ortiz-Maldonado, Joan Cid, Jaime Tabera, Josep M. Canals, Miquel Lozano, Tycho Baumann, Anna Vilarrodona, Esteve Trias, Elías Campo, Pablo Menendez, Álvaro Urbano-Ispizua, Jordi Yagüe, Patricia Pérez-Galán, Susana Rives, Julio Delgado, Manel Juan |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Methods & Clinical Development, Vol 12, Iss , Pp 134-144 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2329-0501 |
| DOI: |
10.1016/j.omtm.2018.11.010 |
| Popis: |
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. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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