| Téléchargement | - Voir la version finale : Multivariate data analysis of process parameters affecting the growth and productivity of stable Chinese hamster ovary cell pools expressing SARS‐CoV ‐2 spike protein as vaccine antigen in early process development (PDF, 3.6 Mio)
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| DOI | Trouver le DOI : https://doi.org/10.1002/btpr.3467 |
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| Auteur | Rechercher : Reyes, Sebastian‐Juan1, 2; Rechercher : Lemire, Lucas1, 2; Rechercher : Molina, Raul‐Santiago3; Rechercher : Roy, Marjolaine1; Rechercher : L'Ecuyer‐Coelho, Helene1; Rechercher : Martynova, Yuliya1; Rechercher : Cass, Brian1; Rechercher : Voyer, Robert1; Rechercher : Durocher, Yves1Identifiant ORCID : https://orcid.org/0000-0002-2268-4111; Rechercher : Henry, Olivier2Identifiant ORCID : https://orcid.org/0000-0003-2106-1331; Rechercher : Pham, Phuong Lan1Identifiant ORCID : https://orcid.org/0000-0002-2390-9730 |
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| Affiliation | - Conseil national de recherches Canada. Thérapeutique en santé humaine
- Department of Chemical Engineering Polytechnique Montreal
- Proelium S.A.S Bogotá Colombia
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| Bailleur de fonds | Rechercher : Natural Sciences and Engineering Research Council of Canada; Rechercher : National Research Council Canada |
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| Format | Texte, Article |
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| Résumé | The recent COVID-19 pandemic revealed an urgent need to develop robust cell culture platforms which can react rapidly to respond to this kind of global health issue. Chinese hamster ovary (CHO) stable pools can be a vital alternative to quickly provide gram amounts of recombinant proteins required for early-phase clinical assays. In this study, we analyze early process development data of recombinant trimeric spike protein Cumate-inducible manufacturing platform utilizing CHO stable pool as a preferred production host across three different stirred-tank bioreactor scales (0.75, 1, and 10 L). The impact of cell passage number as an indicator of cell age, methionine sulfoximine (MSX) concentration as a selection pressure, and cell seeding density was investigated using stable pools expressing three variants of concern. Multivariate data analysis with principal component analysis and batch-wise unfolding technique was applied to evaluate the effect of critical process parameters on production variability and a random forest (RF) model was developed to forecast protein production. In order to further improve process understanding, the RF model was analyzed with Shapley value dependency plots so as to determine what ranges of variables were most associated with increased protein production. Increasing longevity, controlling lactate build-up, and altering pH deadband are considered promising approaches to improve overall culture outcomes. The results also demonstrated that these pools are in general stable expressing similar level of spike proteins up to cell passage 11 (~31 cell generations). This enables to expand enough cells required to seed large volume of 200–2000 L bioreactor. |
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| Date de publication | 2024-04-25 |
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| Maison d’édition | Wiley
American Institute of Chemical Engineers (AIChE) |
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| Licence | |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 1bd13acd-59a9-452b-a292-6ea9434518d4 |
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| Enregistrement créé | 2024-09-18 |
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| Enregistrement modifié | 2025-11-05 |
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