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

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.