AUTHOR=Jackson Zachary , Roe Anne , Sharma Ashish Arunkumar , Lopes Filipa Blasco Tavares Pereira , Talla Aarthi , Kleinsorge-Block Sarah , Zamborsky Kayla , Schiavone Jennifer , Manjappa Shivaprasad , Schauner Robert , Lee Grace , Liu Ruifu , Caimi Paolo F. , Xiong Ying , Krueger Winfried , Worden Andrew , Kadan Mike , Schneider Dina , Orentas Rimas , Dropulic Boro , Sekaly Rafick-Pierre , de Lima Marcos , Wald David N. , Reese Jane S. TITLE=Automated Manufacture of Autologous CD19 CAR-T Cells for Treatment of Non-hodgkin Lymphoma JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01941 DOI=10.3389/fimmu.2020.01941 ISSN=1664-3224 ABSTRACT=

Chimeric antigen receptor T cells (CAR-T cell) targeting CD19 are effective against several subtypes of CD19-expressing hematologic malignancies. Centralized manufacturing has allowed rapid expansion of this cellular therapy, but it may be associated with treatment delays due to the required logistics. We hypothesized that point of care manufacturing of CAR-T cells on the automated CliniMACS Prodigy® device allows reproducible and fast delivery of cells for the treatment of patients with non-Hodgkin lymphoma. Here we describe cell manufacturing results and characterize the phenotype and effector function of CAR-T cells used in a phase I/II study. We utilized a lentiviral vector delivering a second-generation CD19 CAR construct with 4-1BB costimulatory domain and TNFRSF19 transmembrane domain. Our data highlight the successful generation of CAR-T cells at numbers sufficient for all patients treated, a shortened duration of production from 12 to 8 days followed by fresh infusion into patients, and the detection of CAR-T cells in patient circulation up to 1-year post-infusion.