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2018-12-06

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cc-by (c) Castella, Maria et al., 2018
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/147807

Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions

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Recurs relacionat

https://doi.org/10.1016/j.omtm.2018.11.010

Resum

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.

Matèries

Immunoteràpia, Leucèmia, Limfomes, Cèl·lules T

Matèries (anglès)

Immunotheraphy, Leukemia, Lymphomas, T cells

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

CASTELLÀ CASTELLÀ, Maria, et al. Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions. Molecular Therapy-Methods & Clinical Development. 2018. Vol. 12, num. 134-144. ISSN 2329-0501. [consulted: 18 of August of 2026]. Available at: https://hdl.handle.net/2445/147807

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