Development, optimization, and scale-up of suspension Vero cell culture process for high titer production of oncolytic herpes simplex virus-1
© 2023 Wiley-VCH GmbH..
Oncolytic viruses (OVs) have emerged as a novel cancer treatment modality, and four OVs have been approved for cancer immunotherapy. However, high-yield and cost-effective production processes remain to be developed for most OVs. Here suspension-adapted Vero cell culture processes were developed for high titer production of an OV model, herpes simplex virus type 1 (HSV-1). Our study showed the HSV-1 productivity was significantly affected by multiplicity of infection, cell density, and nutritional supplies. Cell culture conditions were first optimized in shake flask experiments and then scaled up to 3 L bioreactors for virus production under batch and perfusion modes. A titer of 2.7 × 108 TCID50 mL-1 was obtained in 3 L batch culture infected at a cell density of 1.4 × 106 cells mL-1 , and was further improved to 1.1 × 109 TCID50 mL-1 in perfusion culture infected at 4.6 × 106 cells mL-1 . These titers are similar to or better than the previously reported best titer of 8.6 × 107 TCID50 mL-1 and 8.1 × 108 TCID50 mL-1 respectively obtained in labor-intensive adherent Vero batch and perfusion cultures. HSV-1 production in batch culture was successfully scaled up to 60 L pilot-scale bioreactor to demonstrate the scalability. The work reported here is the first study demonstrating high titer production of HSV-1 in suspension Vero cell culture under different bioreactor operating modes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Biotechnology journal - 19(2024), 1 vom: 17. Jan., Seite e2300244 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shen, Chun Fang [VerfasserIn] |
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| Links: |
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| Themen: |
Herpes simplex virus |
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| Anmerkungen: |
Date Completed 30.01.2024 Date Revised 30.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/biot.202300244 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Oncolytic viruses (OVs) have emerged as a novel cancer treatment modality, and four OVs have been approved for cancer immunotherapy. However, high-yield and cost-effective production processes remain to be developed for most OVs. Here suspension-adapted Vero cell culture processes were developed for high titer production of an OV model, herpes simplex virus type 1 (HSV-1). Our study showed the HSV-1 productivity was significantly affected by multiplicity of infection, cell density, and nutritional supplies. Cell culture conditions were first optimized in shake flask experiments and then scaled up to 3 L bioreactors for virus production under batch and perfusion modes. A titer of 2.7 × 108 TCID50 mL-1 was obtained in 3 L batch culture infected at a cell density of 1.4 × 106 cells mL-1 , and was further improved to 1.1 × 109 TCID50 mL-1 in perfusion culture infected at 4.6 × 106 cells mL-1 . These titers are similar to or better than the previously reported best titer of 8.6 × 107 TCID50 mL-1 and 8.1 × 108 TCID50 mL-1 respectively obtained in labor-intensive adherent Vero batch and perfusion cultures. HSV-1 production in batch culture was successfully scaled up to 60 L pilot-scale bioreactor to demonstrate the scalability. The work reported here is the first study demonstrating high titer production of HSV-1 in suspension Vero cell culture under different bioreactor operating modes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a herpes simplex virus | |
| 650 | 4 | |a oncolytic viruses | |
| 650 | 4 | |a perfusion culture | |
| 650 | 4 | |a suspension Vero cell | |
| 700 | 1 | |a Burney, Elodie |e verfasserin |4 aut | |
| 700 | 1 | |a Gilbert, Rénald |e verfasserin |4 aut | |
| 700 | 1 | |a Elahi, S Mehdy |e verfasserin |4 aut | |
| 700 | 1 | |a Parato, Kelley |e verfasserin |4 aut | |
| 700 | 1 | |a Loignon, Martin |e verfasserin |4 aut | |
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