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- Voir les données supplémentaires : Isolation of TGF-β-neutralizing single-domain antibodies of predetermined epitope specificity using next-generation DNA sequencing (DOCX, 202 Kio)
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| DOI | Trouver le DOI : https://doi.org/10.1093/protein/gzw043 |
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| Auteur | Rechercher : Henry, Kevin A.1; Rechercher : Hussack, Greg1; Rechercher : Collins, Cathy1; Rechercher : Zwaagstra, John C.1; Rechercher : Tanha, Jamshid1; Rechercher : MacKenzie, C. Roger1 |
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| Affiliation | - Conseil national de recherches du Canada. Thérapeutique en santé humaine
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| Format | Texte, Article |
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| Sujet | antibody; single-domain antibody; VHH; TGF-β; next-generation DNA sequencing; phage display |
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| Résumé | The epitope specificity of therapeutic antibodies is often critical to their efficacy and mode of action. Here, we report the isolation of single-domain antibodies (sdAbs) against a pre-specified epitope of TGF-β3: namely, the site of interaction between the cytokine and its cell-surface type II receptor. By panning a phage-displayed immune llama VhH library against TGF-β3 using competitive elution with soluble dimeric type II receptor ectodomain in tandem with next-generation DNA sequencing, we identified several sdAbs that competed with the receptor for TGF-β3 binding and neutralized TGF-β3 in in vitro cellular assays. In contrast, all other sdAbs identified using conventional panning approaches (i.e., without regard to epitope specificity) did not target the site of receptor:cytokine interaction. We expect this strategy to be generally applicable for identifying epitope-specific sdAbs when binding reagents directed against the epitope of interest are available. The sdAbs identified here are of potential interest as cancer immunotherapeutics. |
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| Date de publication | 2016-09-08 |
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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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| Numéro NPARC | 23000759 |
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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 | 646f2540-63b6-4b0e-a7ae-731f5c2a6082 |
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| Enregistrement créé | 2016-09-14 |
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| Enregistrement modifié | 2020-06-02 |
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