Journal
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
Volume 12, Issue -, Pages 134-144Publisher
CELL PRESS
DOI: 10.1016/j.omtm.2018.11.010
Keywords
-
Categories
Funding
- Plan Nacional de I + D + I [PI13/00676, PIE13/00033, PI17/01043, PICIS14/00122]
- Fondo Europeo de Desarrollo Regional (FEDER)
- European Research Council [CoG-2014-646903, PoC-2018-811220]
- Spanish Ministry of Economy-Competitiveness [SAF2016]
- Catalunya Government [SGR330, PERIS 2017]
- Asociacion Espanola Contra el Cancer (AECC), Beca FERO
- ISCIII/FEDER [PI17/01028]
- Obra Social La Caixa-Fundacio Josep Carreras
- ISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion Sanitaria
- crowd-funding program Projecte ARI
Ask authors/readers for more resources
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-Prkdc(scid) Il2rd(tm1Wjl)/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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available