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NKp46‐specific single domain antibodies enable facile engineering of various potent NK cell engager formats

Lipinski, Britta ; Arras, Paul ; Pekar, Lukas ; Klewinghaus, Daniel ; Boje, Ammelie Svea ; Krah, Simon ; Zimmermann, Jasmin ; Klausz, Katja ; Peipp, Matthias ; Siegmund, Vanessa ; Evers, Andreas ; Zielonka, Stefan (2023)
NKp46‐specific single domain antibodies enable facile engineering of various potent NK cell engager formats.
In: Protein Science, 32 (3)
doi: 10.1002/pro.4593
Artikel, Bibliographie

Dies ist die neueste Version dieses Eintrags.

Kurzbeschreibung (Abstract)

Herein, we describe the generation of potent NK cell engagers (NKCEs) based on single domain antibodies (sdAbs) specific for NKp46 harboring the humanized Fab version of Cetuximab for tumor targeting. After immunization of camelids, a plethora of different VHH domains were retrieved by yeast surface display. Upon reformatting into Fc effector‐silenced NKCEs targeting NKp46 and EGFR in a strictly monovalent fashion, the resulting bispecific antibodies elicited potent NK cell‐mediated killing of EGFR‐overexpressing tumor cells with potencies (EC₅₀killing) in the picomolar range. This was further augmented via co‐engagement of Fcγ receptor IIIa (FcγRIIIa). Importantly, NKp46‐specific sdAbs enabled the construction of various NKCE formats with different geometries and valencies which displayed favorable biophysical and biochemical properties without further optimization. By this means, killing capacities were further improved significantly. Hence, NKp46‐specific sdAbs are versatile building blocks for the construction of different NKCE formats.

Typ des Eintrags: Artikel
Erschienen: 2023
Autor(en): Lipinski, Britta ; Arras, Paul ; Pekar, Lukas ; Klewinghaus, Daniel ; Boje, Ammelie Svea ; Krah, Simon ; Zimmermann, Jasmin ; Klausz, Katja ; Peipp, Matthias ; Siegmund, Vanessa ; Evers, Andreas ; Zielonka, Stefan
Art des Eintrags: Bibliographie
Titel: NKp46‐specific single domain antibodies enable facile engineering of various potent NK cell engager formats
Sprache: Englisch
Publikationsjahr: 2023
Ort: Darmstadt
Verlag: John Wiley & Sons
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Protein Science
Jahrgang/Volume einer Zeitschrift: 32
(Heft-)Nummer: 3
Kollation: 16 Seiten
DOI: 10.1002/pro.4593
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Kurzbeschreibung (Abstract):

Herein, we describe the generation of potent NK cell engagers (NKCEs) based on single domain antibodies (sdAbs) specific for NKp46 harboring the humanized Fab version of Cetuximab for tumor targeting. After immunization of camelids, a plethora of different VHH domains were retrieved by yeast surface display. Upon reformatting into Fc effector‐silenced NKCEs targeting NKp46 and EGFR in a strictly monovalent fashion, the resulting bispecific antibodies elicited potent NK cell‐mediated killing of EGFR‐overexpressing tumor cells with potencies (EC₅₀killing) in the picomolar range. This was further augmented via co‐engagement of Fcγ receptor IIIa (FcγRIIIa). Importantly, NKp46‐specific sdAbs enabled the construction of various NKCE formats with different geometries and valencies which displayed favorable biophysical and biochemical properties without further optimization. By this means, killing capacities were further improved significantly. Hence, NKp46‐specific sdAbs are versatile building blocks for the construction of different NKCE formats.

Freie Schlagworte: ADCC, antibody engineering, bispecific antibody, multifunctional antibody, NK cell engager, NK cell redirection, NKp46, single domain antibody, valencies, VHH
Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 540 Chemie
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit
Fachbereich(e)/-gebiet(e): 07 Fachbereich Chemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut
Hinterlegungsdatum: 02 Aug 2024 12:52
Letzte Änderung: 02 Aug 2024 12:52
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