Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors

Chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated clinical efficacy in treating haematological malignancies, resulting in multiple regulatory approvals. However, there is a need for robust manufacturing platforms and the use of GMP-aligned reagents to meet the clinical and commerc...

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Autores: Silva Couto, Pedro, Stibbs, Dale J., Springuel, Pierre, Schultz, Ursula, Effenberger, Manuel, Goldrick, Stephen, Navarro-Velazquez, Sergio, Juan, Manel, Herbst, Laura, Niessing, Bastian, Mestermann, Katrin, Sanges, Carmen, Hudecek, Michael, Rafiq, Qasim A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p29923
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29923
Access Level:acceso abierto
Palabra clave:ATMP
biomanufacturing
CAR-T
GMP
serum free
stirred-tank bioreactor
xeno-free
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spelling Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank BioreactorsSilva Couto, PedroStibbs, Dale J.Springuel, PierreSchultz, UrsulaEffenberger, ManuelGoldrick, StephenNavarro-Velazquez, SergioJuan, ManelHerbst, LauraNiessing, BastianMestermann, KatrinSanges, CarmenHudecek, MichaelRafiq, Qasim A.ATMPbiomanufacturingCAR-TGMPserum freestirred-tank bioreactorxeno-freeChimeric antigen receptor T-cell (CAR-T) therapies have demonstrated clinical efficacy in treating haematological malignancies, resulting in multiple regulatory approvals. However, there is a need for robust manufacturing platforms and the use of GMP-aligned reagents to meet the clinical and commercial demands. This study investigates the impact of serum/xeno-free medium (SXFM) and cytokine supplementation on CAR-T cell production in static and agitated culture systems, using 24-well plate G-Rex vessels and 500 mL stirred tank bioreactors (STRs), respectively. Under static conditions, SXFM media supported CAR-T cell expansion with growth kinetics comparable to foetal bovine serum, FBS-based RPMI, irrespective of the cytokine supplementation (IL-2 or the combination of IL-7 and IL-15). In contrast, when the expansion was conducted using STRs, several differences were observed with SXFM. Particularly, when supplemented with IL-2 SXFM, it increased transduction efficiency, supporting accelerated proliferation relative to FBS-containing RPMI. Additionally, SXFM maintained a higher CD4:CD8 ratio at harvest, a feature associated with improved clinical outcomes. No significant differences were observed in the CAR-T cell populations' differentiation status or activation and exhaustion profiles across the conditions. These results suggest that SXFM enables CAR-T cell manufacturing in STRs, improving key quality attributes such as transduction efficiency, growth kinetics, and CD4:CD8 ratio compared to FBS-supplemented medium.WILEY-V C H VERLAG GMBH2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29923Biotechnology JournalISSN: 18606768ISSNe: 18607314reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p299232026-05-27T12:37:41Z
dc.title.none.fl_str_mv Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors
title Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors
spellingShingle Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors
Silva Couto, Pedro
ATMP
biomanufacturing
CAR-T
GMP
serum free
stirred-tank bioreactor
xeno-free
title_short Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors
title_full Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors
title_fullStr Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors
title_full_unstemmed Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors
title_sort Impact of Serum/Xeno-Free Medium and Cytokine Supplementation on CAR-T Cell Therapy Manufacturing in Stirred Tank Bioreactors
dc.creator.none.fl_str_mv Silva Couto, Pedro
Stibbs, Dale J.
Springuel, Pierre
Schultz, Ursula
Effenberger, Manuel
Goldrick, Stephen
Navarro-Velazquez, Sergio
Juan, Manel
Herbst, Laura
Niessing, Bastian
Mestermann, Katrin
Sanges, Carmen
Hudecek, Michael
Rafiq, Qasim A.
author Silva Couto, Pedro
author_facet Silva Couto, Pedro
Stibbs, Dale J.
Springuel, Pierre
Schultz, Ursula
Effenberger, Manuel
Goldrick, Stephen
Navarro-Velazquez, Sergio
Juan, Manel
Herbst, Laura
Niessing, Bastian
Mestermann, Katrin
Sanges, Carmen
Hudecek, Michael
Rafiq, Qasim A.
author_role author
author2 Stibbs, Dale J.
Springuel, Pierre
Schultz, Ursula
Effenberger, Manuel
Goldrick, Stephen
Navarro-Velazquez, Sergio
Juan, Manel
Herbst, Laura
Niessing, Bastian
Mestermann, Katrin
Sanges, Carmen
Hudecek, Michael
Rafiq, Qasim A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ATMP
biomanufacturing
CAR-T
GMP
serum free
stirred-tank bioreactor
xeno-free
topic ATMP
biomanufacturing
CAR-T
GMP
serum free
stirred-tank bioreactor
xeno-free
description Chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated clinical efficacy in treating haematological malignancies, resulting in multiple regulatory approvals. However, there is a need for robust manufacturing platforms and the use of GMP-aligned reagents to meet the clinical and commercial demands. This study investigates the impact of serum/xeno-free medium (SXFM) and cytokine supplementation on CAR-T cell production in static and agitated culture systems, using 24-well plate G-Rex vessels and 500 mL stirred tank bioreactors (STRs), respectively. Under static conditions, SXFM media supported CAR-T cell expansion with growth kinetics comparable to foetal bovine serum, FBS-based RPMI, irrespective of the cytokine supplementation (IL-2 or the combination of IL-7 and IL-15). In contrast, when the expansion was conducted using STRs, several differences were observed with SXFM. Particularly, when supplemented with IL-2 SXFM, it increased transduction efficiency, supporting accelerated proliferation relative to FBS-containing RPMI. Additionally, SXFM maintained a higher CD4:CD8 ratio at harvest, a feature associated with improved clinical outcomes. No significant differences were observed in the CAR-T cell populations' differentiation status or activation and exhaustion profiles across the conditions. These results suggest that SXFM enables CAR-T cell manufacturing in STRs, improving key quality attributes such as transduction efficiency, growth kinetics, and CD4:CD8 ratio compared to FBS-supplemented medium.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29923
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29923
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY-V C H VERLAG GMBH
publisher.none.fl_str_mv WILEY-V C H VERLAG GMBH
dc.source.none.fl_str_mv Biotechnology Journal
ISSN: 18606768
ISSNe: 18607314
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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