Formulation Considerations for Autologous T Cell Drug Products
Genetically modified autologous T cells have become an established immunotherapy in the fight against cancer. The manufacture of chimeric antigen receptor (CAR) and αβ-T cell receptor (TCR) transduced T cells poses unique challenges, including the formulation, cryopreservation and fill–finish steps,...
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Format: | Article |
Language: | English |
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MDPI AG
2021-08-01
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Series: | Pharmaceutics |
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Online Access: | https://www.mdpi.com/1999-4923/13/8/1317 |
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author | Christopher F. van der Walle Sonya Godbert Gabriele Saito Zein Azhari |
author_facet | Christopher F. van der Walle Sonya Godbert Gabriele Saito Zein Azhari |
author_sort | Christopher F. van der Walle |
collection | DOAJ |
description | Genetically modified autologous T cells have become an established immunotherapy in the fight against cancer. The manufacture of chimeric antigen receptor (CAR) and αβ-T cell receptor (TCR) transduced T cells poses unique challenges, including the formulation, cryopreservation and fill–finish steps, which are the focus of this review. With an increasing number of marketing approvals for CAR-T cell therapies, comparison of their formulation design and presentation for administration can be made. These differences will be discussed alongside the emergence of automated formulation and fill-finish processes, the formulation design space, Monte Carlo simulation applied to risk analysis, primary container selection, freezing profiles and thaw and the use of dimethyl sulfoxide and alternative solvents/excipients as cryopreservation agents. The review will conclude with a discussion of the pharmaceutical solutions required to meet the simplification of manufacture and flexibility in dosage form for clinical treatment. |
first_indexed | 2024-03-10T08:28:24Z |
format | Article |
id | doaj.art-7e281b717721464ab41da4ccbe753743 |
institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-03-10T08:28:24Z |
publishDate | 2021-08-01 |
publisher | MDPI AG |
record_format | Article |
series | Pharmaceutics |
spelling | doaj.art-7e281b717721464ab41da4ccbe7537432023-11-22T09:16:01ZengMDPI AGPharmaceutics1999-49232021-08-01138131710.3390/pharmaceutics13081317Formulation Considerations for Autologous T Cell Drug ProductsChristopher F. van der Walle0Sonya Godbert1Gabriele Saito2Zein Azhari3GSK R&D, Gunnels Wood, Stevenage, Herts SG1 2NY, UKGSK R&D, Gunnels Wood, Stevenage, Herts SG1 2NY, UKGSK R&D, Gunnels Wood, Stevenage, Herts SG1 2NY, UKGSK R&D, Gunnels Wood, Stevenage, Herts SG1 2NY, UKGenetically modified autologous T cells have become an established immunotherapy in the fight against cancer. The manufacture of chimeric antigen receptor (CAR) and αβ-T cell receptor (TCR) transduced T cells poses unique challenges, including the formulation, cryopreservation and fill–finish steps, which are the focus of this review. With an increasing number of marketing approvals for CAR-T cell therapies, comparison of their formulation design and presentation for administration can be made. These differences will be discussed alongside the emergence of automated formulation and fill-finish processes, the formulation design space, Monte Carlo simulation applied to risk analysis, primary container selection, freezing profiles and thaw and the use of dimethyl sulfoxide and alternative solvents/excipients as cryopreservation agents. The review will conclude with a discussion of the pharmaceutical solutions required to meet the simplification of manufacture and flexibility in dosage form for clinical treatment.https://www.mdpi.com/1999-4923/13/8/1317closed processfill–finishdesign spaceprimary containercryopreservationfreeze–thaw |
spellingShingle | Christopher F. van der Walle Sonya Godbert Gabriele Saito Zein Azhari Formulation Considerations for Autologous T Cell Drug Products Pharmaceutics closed process fill–finish design space primary container cryopreservation freeze–thaw |
title | Formulation Considerations for Autologous T Cell Drug Products |
title_full | Formulation Considerations for Autologous T Cell Drug Products |
title_fullStr | Formulation Considerations for Autologous T Cell Drug Products |
title_full_unstemmed | Formulation Considerations for Autologous T Cell Drug Products |
title_short | Formulation Considerations for Autologous T Cell Drug Products |
title_sort | formulation considerations for autologous t cell drug products |
topic | closed process fill–finish design space primary container cryopreservation freeze–thaw |
url | https://www.mdpi.com/1999-4923/13/8/1317 |
work_keys_str_mv | AT christopherfvanderwalle formulationconsiderationsforautologoustcelldrugproducts AT sonyagodbert formulationconsiderationsforautologoustcelldrugproducts AT gabrielesaito formulationconsiderationsforautologoustcelldrugproducts AT zeinazhari formulationconsiderationsforautologoustcelldrugproducts |