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

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) operat...

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Autores principales:	Seung Mi Yoo, Vivan W.C. Lau, Craig Aarts, Bojana Bojovic, Gregory Steinberg, Joanne A. Hammill, Anna Dvorkin-Gheva, Raja Ghosh, Jonathan L. Bramson
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	engineered t cell manufacturing hollow fiber membrane bioreactor cryopreservation Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/bc99de84057540318ad448278d420b7a
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spelling	oai:doaj.org-article:bc99de84057540318ad448278d420b7a2021-11-11T14:23:43ZManufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency2162-402X10.1080/2162402X.2021.1995168https://doaj.org/article/bc99de84057540318ad448278d420b7a2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/2162402X.2021.1995168https://doaj.org/toc/2162-402XEngineered 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.Seung Mi YooVivan W.C. LauCraig AartsBojana BojovicGregory SteinbergJoanne A. HammillAnna Dvorkin-GhevaRaja GhoshJonathan L. BramsonTaylor & Francis Grouparticleengineered t cellmanufacturinghollow fiber membrane bioreactorcryopreservationImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncoImmunology, Vol 10, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	engineered t cell manufacturing hollow fiber membrane bioreactor cryopreservation Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	engineered t cell manufacturing hollow fiber membrane bioreactor cryopreservation Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Seung Mi Yoo Vivan W.C. Lau Craig Aarts Bojana Bojovic Gregory Steinberg Joanne A. Hammill Anna Dvorkin-Gheva Raja Ghosh Jonathan L. Bramson Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency
description	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.
format	article
author	Seung Mi Yoo Vivan W.C. Lau Craig Aarts Bojana Bojovic Gregory Steinberg Joanne A. Hammill Anna Dvorkin-Gheva Raja Ghosh Jonathan L. Bramson
author_facet	Seung Mi Yoo Vivan W.C. Lau Craig Aarts Bojana Bojovic Gregory Steinberg Joanne A. Hammill Anna Dvorkin-Gheva Raja Ghosh Jonathan L. Bramson
author_sort	Seung Mi Yoo
title	Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency
title_short	Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency
title_full	Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency
title_fullStr	Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency
title_full_unstemmed	Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency
title_sort	manufacturing t cells in hollow fiber membrane bioreactors changes their programming and enhances their potency
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/bc99de84057540318ad448278d420b7a
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Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency

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