Bogen, Jan P. ; Carrara, Stefania C. ; Fiebig, David ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald (2021)
Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening.
In: Frontiers in Immunology, 2020, 11
doi: 10.26083/tuprints-00019264
Article, Secondary publication, Publisher's Version
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Abstract
Bispecific (BsAb) and biparatopic (BpAb) antibodies emerged as promising formats for therapeutic biologics exhibiting tailor-made functional properties. Over recent years, chicken-derived antibodies have gained traction for diagnostic and therapeutic applications due to their broad epitope coverage and convenience of library generation. Here we report the first generation of a biparatopic common light chain (cLC) chicken-derived antibody by an epitope binning-based screening approach using yeast surface display. The resulting monospecific antibodies target conformational epitopes on domain II or III of the epidermal growth factor receptor (EGFR) with lower double- or single-digit nanomolar affinities, respectively. Furthermore, the domain III targeting variant was shown to interfere with epidermal growth factor (EGF) binding. Utilizing the Knob-into-Hole technology (KiH), a biparatopic antibody with subnanomolar affinity was generated that facilitates clustering of soluble and cell-bound EGFR and displayed enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) compared to the parental antibodies. This strategy for generating cLC-based biparatopic antibodies from immunized chickens may pave the way for their further development in therapeutic settings.
| Item Type: | Article |
|---|---|
| Erschienen: | 2021 |
| Creators: | Bogen, Jan P. ; Carrara, Stefania C. ; Fiebig, David ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald |
| Type of entry: | Secondary publication |
| Title: | Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening |
| Language: | English |
| Date: | 2021 |
| Year of primary publication: | 2020 |
| Publisher: | Frontiers |
| Journal or Publication Title: | Frontiers in Immunology |
| Volume of the journal: | 11 |
| Collation: | 13 Seiten |
| DOI: | 10.26083/tuprints-00019264 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/19264 |
| Corresponding Links: | |
| Origin: | Secondary publication via sponsored Golden Open Access |
| Abstract: | Bispecific (BsAb) and biparatopic (BpAb) antibodies emerged as promising formats for therapeutic biologics exhibiting tailor-made functional properties. Over recent years, chicken-derived antibodies have gained traction for diagnostic and therapeutic applications due to their broad epitope coverage and convenience of library generation. Here we report the first generation of a biparatopic common light chain (cLC) chicken-derived antibody by an epitope binning-based screening approach using yeast surface display. The resulting monospecific antibodies target conformational epitopes on domain II or III of the epidermal growth factor receptor (EGFR) with lower double- or single-digit nanomolar affinities, respectively. Furthermore, the domain III targeting variant was shown to interfere with epidermal growth factor (EGF) binding. Utilizing the Knob-into-Hole technology (KiH), a biparatopic antibody with subnanomolar affinity was generated that facilitates clustering of soluble and cell-bound EGFR and displayed enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) compared to the parental antibodies. This strategy for generating cLC-based biparatopic antibodies from immunized chickens may pave the way for their further development in therapeutic settings. |
| Status: | Publisher's Version |
| URN: | urn:nbn:de:tuda-tuprints-192647 |
| Classification DDC: | 500 Science and mathematics > 540 Chemistry |
| Divisions: | 07 Department of Chemistry 07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Department of Chemistry > Clemens-Schöpf-Institut |
| Date Deposited: | 06 Aug 2021 07:25 |
| Last Modified: | 02 Aug 2024 12:35 |
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| Suche nach Titel in: | TUfind oder in Google |
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