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, 2023, 32 (3)
doi: 10.26083/tuprints-00023690
Article, Secondary publication, Publisher's Version
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Item Type: | Article |
---|---|
Type of entry: | Secondary publication |
Title: | NKp46‐specific single domain antibodies enable facile engineering of various potent NK cell engager formats |
Language: | English |
Date: | 12 May 2023 |
Place of Publication: | Darmstadt |
Year of primary publication: | 2023 |
Publisher: | John Wiley & Sons |
Journal or Publication Title: | Protein Science |
Volume of the journal: | 32 |
Issue Number: | 3 |
Collation: | 16 Seiten |
DOI: | 10.26083/tuprints-00023690 |
Corresponding Links: | |
Origin: | Secondary publication DeepGreen |
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. |
Uncontrolled Keywords: | ADCC, antibody engineering, bispecific antibody, multifunctional antibody, NK cell engager, NK cell redirection, NKp46, single domain antibody, valencies, VHH |
Status: | Publisher's Version |
URN: | urn:nbn:de:tuda-tuprints-236908 |
Classification DDC: | 500 Science and mathematics > 540 Chemistry 500 Science and mathematics > 570 Life sciences, biology 600 Technology, medicine, applied sciences > 610 Medicine and health |
Divisions: | 07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie |
Date Deposited: | 12 May 2023 08:47 |
Last Modified: | 14 Nov 2023 19:05 |
SWORD Depositor: | Deep Green |
URI: | https://tuprints.ulb.tu-darmstadt.de/id/eprint/23690 |
PPN: | 509298338 |
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