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, 2024
doi: 10.26083/tuprints-00027605
Article, Secondary publication, Publisher's Version
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| Item Type: | Article |
|---|---|
| Type of entry: | Secondary publication |
| Title: | 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 |
| Language: | English |
| Date: | 2 July 2024 |
| Place of Publication: | Darmstadt |
| Year of primary publication: | 2024 |
| Place of primary publication: | Berlin [u.a.] |
| Publisher: | De Gruyter |
| Journal or Publication Title: | Biological Chemistry |
| Collation: | 10 Seiten |
| DOI: | 10.26083/tuprints-00027605 |
| Corresponding Links: | |
| Origin: | Secondary publication service |
| 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. |
| Uncontrolled Keywords: | antibody display, antibody engineering, antibody valency, biparatopic antibody, bovine ultralong CDR-H3 antibody, Fcknob |
| Status: | Publisher's Version |
| URN: | urn:nbn:de:tuda-tuprints-276052 |
| Additional Information: | Ahead of Print (aop) Version |
| Classification DDC: | 500 Science and mathematics > 540 Chemistry 500 Science and mathematics > 570 Life sciences, biology |
| Divisions: | 07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie |
| Date Deposited: | 02 Jul 2024 12:22 |
| Last Modified: | 04 Jul 2024 09:29 |
| URI: | https://tuprints.ulb.tu-darmstadt.de/id/eprint/27605 |
| PPN: | 519526562 |
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