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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, 14
doi: 10.3389/fimmu.2023.1170042
Artikel, Bibliographie

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Kurzbeschreibung (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.

Typ des Eintrags: Artikel
Erschienen: 2023
Autor(en): Harwardt, Julia ; Carrara, Stefania C. ; Bogen, Jan P. ; Schoenfeld, Katrin ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald
Art des Eintrags: Bibliographie
Titel: Generation of a symmetrical trispecific NK cell engager based on a two-in-one antibody
Sprache: Englisch
Publikationsjahr: 2023
Ort: Darmstadt
Verlag: Frontiers Media S.A.
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Frontiers in Immunology
Jahrgang/Volume einer Zeitschrift: 14
Kollation: 13 Seiten
DOI: 10.3389/fimmu.2023.1170042
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Kurzbeschreibung (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.

Freie Schlagworte: trispecific antibody, two-in-one antibody, NK cell engager, common light chain, yeast surface display
Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 540 Chemie
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Fachbereich(e)/-gebiet(e): Interdisziplinäre Forschungsprojekte
Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
07 Fachbereich Chemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut
Hinterlegungsdatum: 02 Aug 2024 12:51
Letzte Änderung: 02 Aug 2024 12:51
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