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• W3036005688 abstract "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 × 10 6 cells/ml. The distribution of CD8+ central memory T cells (T CM ), 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." @default.
• W3036005688 created "2020-06-25" @default.
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• W3036005688 date "2020-07-06" @default.
• W3036005688 modified "2023-10-15" @default.
• W3036005688 title "Bioprocess considerations for T‐cell therapy: Investigating the impact of agitation, dissolved oxygen, and pH on T‐cell expansion and differentiation" @default.
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• W3036005688 doi "https://doi.org/10.1002/bit.27468" @default.
• W3036005688 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32568407" @default.
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