A humanized CD3ε-knock-in mouse model for pre-clinical testing of anti-human CD3 therapy
Pre-clinical murine models are critical for translating drug candidates from the bench to the bedside. There is interest in better understanding how anti-human CD3 therapy works based on recent longitudinal studies of short-term administration. Although several models have been created in this pursuit, each have their own advantages and disadvantages in Type-1 diabetes. In this study, we report a murine genetic knock-in model which expresses both a murine and a humanized-CD3ε-exon, rendering it sensitive to manipulation with anti-human CD3. These huCD3εHET mice are viable and display no gross abnormalities. Specifically, thymocyte development and T cell peripheral homeostasis is unaffected. We tested immune functionality of these mice by immunizing them with T cell-dependent antigens and no differences in antibody titers compared to wild type mice were recorded. Finally, we performed a graft-vs-host disease model that is driven by effector T cell responses and observed a wasting disease upon transfer of huCD3εHET T cells. Our results show a viable humanized CD3 murine model that develops normally, is functionally engaged by anti-human CD3 and can instruct on pre-clinical tests of anti-human CD3 antibodies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
PloS one - 16(2021), 2 vom: 17., Seite e0245917 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Crespo, Joel [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal |
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| Anmerkungen: |
Date Completed 27.07.2021 Date Revised 27.07.2021 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0245917 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 2 | |a A humanized CD3ε-knock-in mouse model for pre-clinical testing of anti-human CD3 therapy |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Pre-clinical murine models are critical for translating drug candidates from the bench to the bedside. There is interest in better understanding how anti-human CD3 therapy works based on recent longitudinal studies of short-term administration. Although several models have been created in this pursuit, each have their own advantages and disadvantages in Type-1 diabetes. In this study, we report a murine genetic knock-in model which expresses both a murine and a humanized-CD3ε-exon, rendering it sensitive to manipulation with anti-human CD3. These huCD3εHET mice are viable and display no gross abnormalities. Specifically, thymocyte development and T cell peripheral homeostasis is unaffected. We tested immune functionality of these mice by immunizing them with T cell-dependent antigens and no differences in antibody titers compared to wild type mice were recorded. Finally, we performed a graft-vs-host disease model that is driven by effector T cell responses and observed a wasting disease upon transfer of huCD3εHET T cells. Our results show a viable humanized CD3 murine model that develops normally, is functionally engaged by anti-human CD3 and can instruct on pre-clinical tests of anti-human CD3 antibodies | ||
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| 700 | 1 | |a Hu, Ningjie |e verfasserin |4 aut | |
| 700 | 1 | |a Moore, Paul A |e verfasserin |4 aut | |
| 700 | 1 | |a Bonvini, Ezio |e verfasserin |4 aut | |
| 700 | 1 | |a Glasebrook, Andrew L |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Andrea P |e verfasserin |4 aut | |
| 700 | 1 | |a Benschop, Robert J |e verfasserin |4 aut | |
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