Castellà Castellà, MariaBoronat, AnnaMartín Ibáñez, RaquelRodríguez, VaninaSuñé, GuillermoCaballero, MiguelMarzal Martí, BertaPérez-Amill, LorenaMartín-Antonio, BeatrizCastaño, JulioBueno, ClaraBalagué, OlgaGonzález-Navarro, Europa AzucenaSerra Pagès, CarlesEngel Rocamora, PabloVilella, RamonBenítez-Ribas, DanielOrtiz-Maldonado Gibson, ValentínCid Vidal, JoanTabera, JaimeCanals i Coll, Josep M.Lozano, MiquelBaumann, TychoVilarrodona, AnnaTrias, EsteveCampo Güerri, EliasMenéndez Buján, PabloUrbano Ispizua, ÁlvaroYagüe, JordiPérez Galán, PatriciaRives Solà, SusanaDelgado, Julio (Delgado González)Juan, Manel2020-01-142020-01-142018-12-062329-0501https://hdl.handle.net/2445/147807Genetically 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.11 p.application/pdfengcc-by (c) Castella, Maria et al., 2018http://creativecommons.org/licenses/by/3.0/esImmunoteràpiaLeucèmiaLimfomesCèl·lules TImmunotheraphyLeukemiaLymphomasT cellsinfo:eu-repo/semantics/article6848892020-01-14info:eu-repo/semantics/openAccess414837830623002