Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency.

Autor:	Yoo SM; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.; Triumvira Immunologics, Hamilton, On, Canada., Lau VWC; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.; Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK., Aarts C; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada., Bojovic B; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada., Steinberg G; Centre for Metabolism, Obesity and Diabetes Research, Department of Medicine, McMaster University, Hamilton, On, Canada., Hammill JA; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada., Dvorkin-Gheva A; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada., Ghosh R; Department of Chemical Engineering, McMaster University, Hamilton, On, Canada., Bramson JL; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2021 Nov 09; Vol. 10 (1), pp. 1995168. Date of Electronic Publication: 2021 Nov 09 (Print Publication: 2021).
DOI:	10.1080/2162402X.2021.1995168
Abstrakt:	Engineered T cell therapies have revolutionized modern oncology, however processes for manufacturing T cell therapies vary and the impact of manufacturing processes On the cell product is poorly understood. Herein, we have used a commercially available hollow fiber membrane bioreactor (HFMBR) operated in a novel mode to demonstrate that T cells can be engineered with lentiviruses, grown to very high densities, and washed and harvested in a single, small volume bioreactor that is readily amenable to automation. Manufacturing within the HFMBR dramatically changed the programming of the T cells and yielded a product with greater therapeutic potency than T cells produced using the standard manual method. This change in programming was associated with increased resistance to cryopreservation, which is beneficial as T cell products are typically cryopreserved prior to administration to the patient. Transcriptional profiling of the T cells revealed a shift toward a glycolytic metabolism, which may protect cells from oxidative stress offering an explanation for the improved resistance to cryopreservation. This study reveals that the choice of bioreactor fundamentally impacts the engineered T cell product and must be carefully considered. Furthermore, these data challenge the premise that glycolytic metabolism is detrimental to T cell therapies. Competing Interests: J.A.H. is a co-inventor on several patents related to chimeric receptors. J.L.B. is a co-inventor on several patents related to chimeric receptors and oncolytic viruses. J.L.B. has ownership interest in and receives research funding from Triumvira Immunologics. The other authors declare no competing interests. (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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