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Generation of a symmetrical trispecific NK cell engager based on a two-in-one antibody

Harwardt, Julia ; Carrara, Stefania C. ; Bogen, Jan P. ; Schoenfeld, Katrin ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald (2023)
Generation of a symmetrical trispecific NK cell engager based on a two-in-one antibody.
In: Frontiers in Immunology, 2023, 14
doi: 10.26083/tuprints-00023673
Article, Secondary publication, Publisher's Version

Abstract

To construct a trispecific IgG-like antibody at least three different binding moieties need to be combined, which results in a complex architecture and challenging production of these molecules. Here we report for the first time the construction of trispecific natural killer cell engagers based on a previously reported two-in-one antibody combined with a novel anti-CD16a common light chain module identified by yeast surface display (YSD) screening of chicken-derived immune libraries. The resulting antibodies simultaneously target epidermal growth factor receptor (EGFR), programmed death-ligand 1 (PD-L1) and CD16a with two Fab fragments, resulting in specific cellular binding properties on EGFR/PD-L1 double positive tumor cells and a potent ADCC effect. This study paves the way for further development of multispecific therapeutic antibodies derived from avian immunization with desired target combinations, valencies, molecular symmetries and architectures.

Item Type: Article
Erschienen: 2023
Creators: Harwardt, Julia ; Carrara, Stefania C. ; Bogen, Jan P. ; Schoenfeld, Katrin ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald
Type of entry: Secondary publication
Title: Generation of a symmetrical trispecific NK cell engager based on a two-in-one antibody
Language: English
Date: 2023
Place of Publication: Darmstadt
Year of primary publication: 2023
Publisher: Frontiers Media S.A.
Journal or Publication Title: Frontiers in Immunology
Volume of the journal: 14
Collation: 13 Seiten
DOI: 10.26083/tuprints-00023673
URL / URN: https://tuprints.ulb.tu-darmstadt.de/23673
Corresponding Links:
Origin: Secondary publication DeepGreen
Abstract:

To construct a trispecific IgG-like antibody at least three different binding moieties need to be combined, which results in a complex architecture and challenging production of these molecules. Here we report for the first time the construction of trispecific natural killer cell engagers based on a previously reported two-in-one antibody combined with a novel anti-CD16a common light chain module identified by yeast surface display (YSD) screening of chicken-derived immune libraries. The resulting antibodies simultaneously target epidermal growth factor receptor (EGFR), programmed death-ligand 1 (PD-L1) and CD16a with two Fab fragments, resulting in specific cellular binding properties on EGFR/PD-L1 double positive tumor cells and a potent ADCC effect. This study paves the way for further development of multispecific therapeutic antibodies derived from avian immunization with desired target combinations, valencies, molecular symmetries and architectures.

Uncontrolled Keywords: trispecific antibody, two-in-one antibody, NK cell engager, common light chain, yeast surface display
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-236733
Classification DDC: 500 Science and mathematics > 540 Chemistry
500 Science and mathematics > 570 Life sciences, biology
Divisions: Interdisziplinäre Forschungsprojekte
Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
07 Department of Chemistry
07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie
Date Deposited: 18 Apr 2023 11:05
Last Modified: 19 Apr 2023 05:00
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