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Demonstrating the Manufacture of Human CAR-T Cells in an Automated Stirred-Tank Bioreactor

Costariol, E; Rotondi, MC; Amini, A; Hewitt, CJ; Nienow, AW; Heathman, TRJ; Rafiq, QA; (2020) Demonstrating the Manufacture of Human CAR-T Cells in an Automated Stirred-Tank Bioreactor. Biotechnology Journal , 15 (9) , Article 2000177. 10.1002/biot.202000177. Green open access

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Abstract

Chimeric antigen receptor T‐cell (CAR‐T) therapies have proven clinical efficacy for the treatment of hematological malignancies. However, CAR‐T cell therapies are prohibitively expensive to manufacture. The authors demonstrate the manufacture of human CAR‐T cells from multiple donors in an automated stirred‐tank bioreactor. The authors successfully produced functional human CAR‐T cells from multiple donors under dynamic conditions in a stirred‐tank bioreactor, resulting in overall cell yields which were significantly better than in static T‐flask culture. At agitation speeds of 200 rpm and greater (up to 500 rpm), the CAR‐T cells are able to proliferate effectively, reaching viable cell densities of >5 × 10^{6} cells ml‐1 over 7 days. This is comparable with current expansion systems and significantly better than static expansion platforms (T‐flasks and gas‐permeable culture bags). Importantly, engineered T‐cells post‐expansion retained expression of the CAR gene and retained their cytolytic function even when grown at the highest agitation intensity. This proves that power inputs used in this study do not affect cell efficacy to target and kill the leukemia cells. This is the first demonstration of human CAR‐T cell manufacture in stirred‐tank bioreactors and the findings present significant implications and opportunities for larger‐scale allogeneic CAR‐T production.

Type: Article
Title: Demonstrating the Manufacture of Human CAR-T Cells in an Automated Stirred-Tank Bioreactor
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/biot.202000177
Publisher version: https://doi.org/10.1002/biot.202000177
Language: English
Additional information: © 2020 The Authors. Biotechnology Journal published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: CAR-T cells, bioprocessing, immunotherapy, manufacture, stirred-tank bioreactor
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10106375
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