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Bioprocess considerations for T cell therapy: Investigating the impact of agitation, dissolved oxygen and pH on T cell expansion and differentiation

Amini, A; Wiegmann, V; Patel, H; Veraitch, F; Baganz, F; (2020) Bioprocess considerations for T cell therapy: Investigating the impact of agitation, dissolved oxygen and pH on T cell expansion and differentiation. Biotechnology and Bioengineering , 117 (10) pp. 3018-3028. 10.1002/bit.27468. Green open access

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Abstract

Adoptive T‐cell therapy (ACT) has emerged as a promising new way to treat systemic cancers such as acute lymphoblastic leukemia. However, the robustness and reproducibility of the manufacturing process remains a challenge. Here, a single‐use 24‐well microbioreactor (micro‐Matrix) was assessed for its use as a high‐throughput screening tool to investigate the effect and the interaction of different shaking speeds, dissolved oxygen (DO), and pH levels on the growth and differentiation of primary T cells in a perfusion‐mimic process. The full factorial design allowed for the generation of predictive models, which were used to find optimal culture conditions. Agitation was shown to play a fundamental role in the proliferation of T cells. A shaking speed of 200 rpm drastically improved the final viable cell concentration (VCC), while the viability was maintained above 90% throughout the cultivation. VCCs reached a maximum of 9.22 × 106 cells/ml. The distribution of CD8+ central memory T cells (TCM), was found to be largely unaffected by the shaking speed. A clear interaction between pH and DO (p < .001) was established for the cell growth and the optimal culture conditions were identified for a combination of 200 rpm, 25% DO, and pH of 7.4. The combination of microbioreactor technology and Design of Experiment methodology provides a powerful tool to rapidly gain an understanding of the design space of the T‐cell manufacturing process.

Type: Article
Title: Bioprocess considerations for T cell therapy: Investigating the impact of agitation, dissolved oxygen and pH on T cell expansion and differentiation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/bit.27468
Publisher version: https://doi.org/10.1002/bit.27468
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10103814
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