Arras, Paul ; Zimmermann, Jasmin ; Lipinski, Britta ; Valldorf, Bernhard ; Evers, Andreas ; Elter, Desislava ; Krah, Simon ; Doerner, Achim ; Guarnera, Enrico ; Siegmund, Vanessa ; Kolmar, Harald ; Pekar, Lukas ; Zielonka, Stefan (2024)
Bovine ultralong CDR-H3 derived knob paratopes elicit potent TNF-α neutralization and enable the generation of novel adalimumab-based antibody architectures with augmented features.
In: Biological Chemistry
doi: 10.1515/hsz-2023-0370
Artikel, Bibliographie
Dies ist die neueste Version dieses Eintrags.
Kurzbeschreibung (Abstract)
In this work we have generated cattle-derived chimeric ultralong CDR-H3 antibodies targeting tumor necrosis factor α (TNF-α) via immunization and yeast surface display. We identified one particular ultralong CDR-H3 paratope that potently neutralized TNF-α. Interestingly, grafting of the knob architecture onto a peripheral loop of the CH₃ domain of the Fc part of an IgG1 resulted in the generation of a TNF-α neutralizing Fc (Fcknob) that did not show any potency loss compared with the parental chimeric IgG format. Eventually, grafting this knob onto the CH₃ region of adalimumab enabled the engineering of a novel TNF-α targeting antibody architecture displaying augmented TNF-α inhibition.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Arras, Paul ; Zimmermann, Jasmin ; Lipinski, Britta ; Valldorf, Bernhard ; Evers, Andreas ; Elter, Desislava ; Krah, Simon ; Doerner, Achim ; Guarnera, Enrico ; Siegmund, Vanessa ; Kolmar, Harald ; Pekar, Lukas ; Zielonka, Stefan |
| Art des Eintrags: | Bibliographie |
| Titel: | Bovine ultralong CDR-H3 derived knob paratopes elicit potent TNF-α neutralization and enable the generation of novel adalimumab-based antibody architectures with augmented features |
| Sprache: | Englisch |
| Publikationsjahr: | 2024 |
| Ort: | Berlin [u.a.] |
| Verlag: | De Gruyter |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Biological Chemistry |
| Kollation: | 10 Seiten |
| DOI: | 10.1515/hsz-2023-0370 |
| Zugehörige Links: | |
| Kurzbeschreibung (Abstract): | In this work we have generated cattle-derived chimeric ultralong CDR-H3 antibodies targeting tumor necrosis factor α (TNF-α) via immunization and yeast surface display. We identified one particular ultralong CDR-H3 paratope that potently neutralized TNF-α. Interestingly, grafting of the knob architecture onto a peripheral loop of the CH₃ domain of the Fc part of an IgG1 resulted in the generation of a TNF-α neutralizing Fc (Fcknob) that did not show any potency loss compared with the parental chimeric IgG format. Eventually, grafting this knob onto the CH₃ region of adalimumab enabled the engineering of a novel TNF-α targeting antibody architecture displaying augmented TNF-α inhibition. |
| Freie Schlagworte: | antibody display, antibody engineering, antibody valency, biparatopic antibody, bovine ultralong CDR-H3 antibody, Fcknob |
| Zusätzliche Informationen: | Ahead of Print (aop) Version |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 03 Jul 2024 11:13 |
| Letzte Änderung: | 03 Jul 2024 11:13 |
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| Suche nach Titel in: | TUfind oder in Google |
Verfügbare Versionen dieses Eintrags
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Bovine ultralong CDR-H3 derived knob paratopes elicit potent TNF-α neutralization and enable the generation of novel adalimumab-based antibody architectures with augmented features. (deposited 02 Jul 2024 12:22)
- Bovine ultralong CDR-H3 derived knob paratopes elicit potent TNF-α neutralization and enable the generation of novel adalimumab-based antibody architectures with augmented features. (deposited 03 Jul 2024 11:13) [Gegenwärtig angezeigt]
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