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

Frontiers in Immunology

卷:11

Jan P. Bogen¹  David Fiebig¹  Julius Grzeschik¹  Stefania C. Carrara¹  Björn Hock²  Harald Kolmar³ 

[1] Ferring Darmstadt Laboratory, Biologics Technology and Development, Darmstadt, Germany;

[2] Ferring International Center S.A., Saint-Prex, Switzerland;

[3] Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, Germany;

关键词: biparatopic antibody;    antibody discovery;    common light chain;    yeast display;    chicken-derived;   

DOI  :  10.3389/fimmu.2020.606878

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown