Lock, Dominik, Mockel-Tenbrinck, Nadine, Drechsel, Katharina, Barth, Carola, Mauer, Daniela, Schaser, Thomas, Kolbe, Carolin, Al Rawashdeh, Wael, Brauner, Janina, Hardt, Olaf, Pflug, Natali, Holtick, Udo, Borchmann, Peter, Assenmacher, Mario and Kaiser, Andrew (2017). Automated Manufacturing of Potent CD20-Directed Chimeric Antigen Receptor T Cells for Clinical Use. Hum. Gene Ther., 28 (10). S. 914 - 926. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-7422

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Abstract

The clinical success of gene-engineered T cells expressing a chimeric antigen receptor (CAR), as manifested in several clinical trials for the treatment of B cell malignancies, warrants the development of a simple and robust manufacturing procedure capable of reducing to a minimum the challenges associated with its complexity. Conventional protocols comprise many open handling steps, are labor intensive, and are difficult to upscale for large numbers of patients. Furthermore, extensive training of personnel is required to avoid operator variations. An automated current Good Manufacturing Practice-compliant process has therefore been developed for the generation of gene-engineered T cells. Upon installation of the closed, single-use tubing set on the CliniMACS Prodigy, sterile welding of the starting cell product, and sterile connection of the required reagents, T cells are magnetically enriched, stimulated, transduced using lentiviral vectors, expanded, and formulated. Starting from healthy donor (HD) or lymphoma or melanoma patient material (PM), the robustness and reproducibility of the manufacturing of anti-CD20 specific CAR T cells were verified. Independent of the starting material, operator, or device, the process consistently yielded a therapeutic dose of highly viable CAR T cells. Interestingly, the formulated product obtained with PM was comparable to that of HD with respect to cell composition, phenotype, and function, even though the starting material differed significantly. Potent antitumor reactivity of the produced anti-CD20 CAR T cells was shown in vitro as well as in vivo. In summary, the automated T cell transduction process meets the requirements for clinical manufacturing that the authors intend to use in two separate clinical trials for the treatment of melanoma and B cell lymphoma.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lock, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mockel-Tenbrinck, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drechsel, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barth, CarolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauer, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaser, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolbe, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al Rawashdeh, WaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brauner, JaninaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hardt, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pflug, NataliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holtick, UdoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borchmann, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assenmacher, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-216657
DOI: 10.1089/hum.2017.111
Journal or Publication Title: Hum. Gene Ther.
Volume: 28
Number: 10
Page Range: S. 914 - 926
Date: 2017
Publisher: MARY ANN LIEBERT, INC
Place of Publication: NEW ROCHELLE
ISSN: 1557-7422
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ADOPTIVE IMMUNOTHERAPY; LYMPHOMA; THERAPY; RITUXIMAB; LEUKEMIA; MEMORY; SCALE; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; MALIGNANCIESMultiple languages
Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21665

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