Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.606878/full |
| _version_ | 1818589994650959872 |
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| author | Jan P. Bogen Jan P. Bogen Stefania C. Carrara Stefania C. Carrara David Fiebig David Fiebig Julius Grzeschik Björn Hock Harald Kolmar |
| author_facet | Jan P. Bogen Jan P. Bogen Stefania C. Carrara Stefania C. Carrara David Fiebig David Fiebig Julius Grzeschik Björn Hock Harald Kolmar |
| author_sort | Jan P. Bogen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T09:49:29Z |
| format | Article |
| id | doaj.art-3f3672396f1b46d3abe7207446757a2f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T09:49:29Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3f3672396f1b46d3abe7207446757a2f2022-12-21T22:36:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.606878606878Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display ScreeningJan P. Bogen0Jan P. Bogen1Stefania C. Carrara2Stefania C. Carrara3David Fiebig4David Fiebig5Julius Grzeschik6Björn Hock7Harald Kolmar8Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, GermanyFerring Darmstadt Laboratory, Biologics Technology and Development, Darmstadt, GermanyInstitute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, GermanyFerring Darmstadt Laboratory, Biologics Technology and Development, Darmstadt, GermanyInstitute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, GermanyFerring Darmstadt Laboratory, Biologics Technology and Development, Darmstadt, GermanyFerring Darmstadt Laboratory, Biologics Technology and Development, Darmstadt, GermanyFerring International Center S.A., Saint-Prex, SwitzerlandInstitute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, GermanyBispecific (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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.606878/fullbiparatopic antibodyantibody discoverycommon light chainyeast displaychicken-derived |
| spellingShingle | Jan P. Bogen Jan P. Bogen Stefania C. Carrara Stefania C. Carrara David Fiebig David Fiebig Julius Grzeschik Björn Hock Harald Kolmar Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening Frontiers in Immunology biparatopic antibody antibody discovery common light chain yeast display chicken-derived |
| title | Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening |
| title_full | Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening |
| title_fullStr | Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening |
| title_full_unstemmed | Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening |
| title_short | Expeditious Generation of Biparatopic Common Light Chain Antibodies via Chicken Immunization and Yeast Display Screening |
| title_sort | expeditious generation of biparatopic common light chain antibodies via chicken immunization and yeast display screening |
| topic | biparatopic antibody antibody discovery common light chain yeast display chicken-derived |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.606878/full |
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