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Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening

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. (Publisher's Version)
In: Frontiers in Immunology, 11, Frontiers, ISSN 1664-3224,
DOI: 10.26083/tuprints-00019264,
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Item Type: Article
Origin: Secondary publication via sponsored Golden Open Access
Status: Publisher's Version
Title: Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening
Language: English
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.

Journal or Publication Title: Frontiers in Immunology
Journal volume: 11
Publisher: Frontiers
Collation: 13 Seiten
Classification DDC: 500 Naturwissenschaften und Mathematik > 540 Chemie
Divisions: 07 Department of Chemistry > Fachgebiet Biochemie
Date Deposited: 06 Aug 2021 07:25
Last Modified: 06 Aug 2021 07:26
DOI: 10.26083/tuprints-00019264
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-192647
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/19264
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