Closing the system : production of viral antigen-presenting dendritic cells eliciting specific CD8+ T cell activation in fluorinated ethylene propylene cell culture bags
BACKGROUND: A major obstacle to anti-viral and -tumor cell vaccination and T cell immunotherapy is the ability to produce dendritic cells (DCs) in a suitable clinical setting. It is imperative to develop closed cell culture systems to accelerate the translation of promising DC-based cell therapy products to the clinic. The objective of this study was to investigate whether viral antigen-loaded monocyte-derived DCs (Mo-DCs) capable of eliciting specific T cell activation can be manufactured in fluorinated ethylene propylene (FEP) bags.
METHODS: Mo-DCs were generated through a protocol applying cytokine cocktails combined with lipopolysaccharide or with a CMV viral peptide antigen in conventional tissue culture polystyrene (TCPS) or FEP culture vessels. Research-scale (< 10 mL) FEP bags were implemented to increase R&D throughput. DC surface marker profiles, cytokine production, and ability to activate antigen-specific cytotoxic T cells were characterized.
RESULTS: Monocyte differentiation into Mo-DCs led to the loss of CD14 expression with concomitant upregulation of CD80, CD83 and CD86. Significantly increased levels of IL-10 and IL-12 were observed after maturation on day 9. Antigen-pulsed Mo-DCs activated antigen-responsive CD8+ cytotoxic T cells. No significant differences in surface marker expression or tetramer-specific T cell activating potency of Mo-DCs were observed between TCPS and FEP culture vessels.
CONCLUSIONS: Our findings demonstrate that viral antigen-loaded Mo-DCs produced in downscaled FEP bags can elicit specific T cell responses. In view of the dire clinical need for closed system DC manufacturing, FEP bags represent an attractive option to accelerate the translation of promising emerging DC-based immunotherapies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Journal of translational medicine - 18(2020), 1 vom: 09. Okt., Seite 383 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bastien, Jean-Philippe [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.05.2021 Date Revised 14.05.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12967-020-02543-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316065684 |
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| 041 | |a eng | ||
| 100 | 1 | |a Bastien, Jean-Philippe |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Closing the system |b production of viral antigen-presenting dendritic cells eliciting specific CD8+ T cell activation in fluorinated ethylene propylene cell culture bags |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 14.05.2021 | ||
| 500 | |a Date Revised 14.05.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: A major obstacle to anti-viral and -tumor cell vaccination and T cell immunotherapy is the ability to produce dendritic cells (DCs) in a suitable clinical setting. It is imperative to develop closed cell culture systems to accelerate the translation of promising DC-based cell therapy products to the clinic. The objective of this study was to investigate whether viral antigen-loaded monocyte-derived DCs (Mo-DCs) capable of eliciting specific T cell activation can be manufactured in fluorinated ethylene propylene (FEP) bags | ||
| 520 | |a METHODS: Mo-DCs were generated through a protocol applying cytokine cocktails combined with lipopolysaccharide or with a CMV viral peptide antigen in conventional tissue culture polystyrene (TCPS) or FEP culture vessels. Research-scale (< 10 mL) FEP bags were implemented to increase R&D throughput. DC surface marker profiles, cytokine production, and ability to activate antigen-specific cytotoxic T cells were characterized | ||
| 520 | |a RESULTS: Monocyte differentiation into Mo-DCs led to the loss of CD14 expression with concomitant upregulation of CD80, CD83 and CD86. Significantly increased levels of IL-10 and IL-12 were observed after maturation on day 9. Antigen-pulsed Mo-DCs activated antigen-responsive CD8+ cytotoxic T cells. No significant differences in surface marker expression or tetramer-specific T cell activating potency of Mo-DCs were observed between TCPS and FEP culture vessels | ||
| 520 | |a CONCLUSIONS: Our findings demonstrate that viral antigen-loaded Mo-DCs produced in downscaled FEP bags can elicit specific T cell responses. In view of the dire clinical need for closed system DC manufacturing, FEP bags represent an attractive option to accelerate the translation of promising emerging DC-based immunotherapies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cellular therapy | |
| 650 | 4 | |a Dendritic cell | |
| 650 | 4 | |a Fluorinated polymers | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Monocyte | |
| 650 | 4 | |a Polystyrene | |
| 650 | 4 | |a Scale-down | |
| 650 | 7 | |a Antigens, Viral |2 NLM | |
| 650 | 7 | |a fluorinated ethylene propylene |2 NLM | |
| 650 | 7 | |a Polytetrafluoroethylene |2 NLM | |
| 650 | 7 | |a 9002-84-0 |2 NLM | |
| 700 | 1 | |a Fekete, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Beland, Ariane V |e verfasserin |4 aut | |
| 700 | 1 | |a Lachambre, Marie-Paule |e verfasserin |4 aut | |
| 700 | 1 | |a Laforte, Veronique |e verfasserin |4 aut | |
| 700 | 1 | |a Juncker, David |e verfasserin |4 aut | |
| 700 | 1 | |a Dave, Vibhuti |e verfasserin |4 aut | |
| 700 | 1 | |a Roy, Denis-Claude |e verfasserin |4 aut | |
| 700 | 1 | |a Hoesli, Corinne A |e verfasserin |4 aut | |
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