title: A Rapid Cell Expansion Process for Production of Engineered Autologous CAR-T Cell Therapies.
abstract: The treatment of B-cell malignancies by adoptive cell transfer (ACT) of anti-CD19 chimeric antigen receptor T cells (CD19 CAR-T) has proven to be a highly successful therapeutic modality in several clinical trials.1-6The anti-CD19 CAR-T cell production method used to support initial trials relied on numerous manual, open process steps, human serum, and 10 days of cell culture to achieve a clinical dose.7This approach limited the ability to support large multicenter clinical trials, as well as scale up for commercial cell production. Therefore, studies were completed to streamline and optimize the original National Cancer Institute production process by removing human serum from the process in order to minimize the risk of viral contamination, moving process steps from an open system to functionally closed system operations in order to minimize the risk of microbial contamination, and standardizing additional process steps in order to maximize process consistency. This study reports a procedure for generating CD19 CAR-T cells in 6 days, using a functionally closed manufacturing process and defined, serum-free medium. This method is able to produce CD19 CAR-T cells that are phenotypically and functionally indistinguishable from cells produced for clinical trials by the previously described production process.
authors.affiliation: 1 Surgery Branch, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors.forename: Tangying Lily
authors.initials: TL
authors.lastname: Lu
authors.affiliation: 2 ImaginAb, Inc. , Inglewood, California.|4 KITE Pharma , Santa Monica, California.
authors.forename: Omar
authors.initials: O
authors.lastname: Pugach
authors.affiliation: 1 Surgery Branch, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Somerville
authors.affiliation: 1 Surgery Branch, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.affiliation: 3 Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors.forename: James N
authors.initials: JN
authors.lastname: Kochenderfer
authors.affiliation: 4 KITE Pharma , Santa Monica, California.
authors.forename: Marc
authors.initials: M
authors.lastname: Better
authors.affiliation: 1 Surgery Branch, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Feldman
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D064987:Cell- and Tissue-Based Therapy; D002986:Clinical Trials as Topic; D016895:Culture Media, Serum-Free; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
chemical_list: D018941:Antigens, CD19; D016895:Culture Media, Serum-Free; D011948:Receptors, Antigen, T-Cell
keywords: GMP; anti-CD19 CAR; closed system; cryopreservation; expansion; transduction