TU Darmstadt / ULB / TUbiblio

Potent apoptosis induction by a novel trispecific B7-H3xCD16xTIGIT 2+1 common light chain natural killer cell engager

Ulitzka, Michael ; Harwardt, Julia ; Lipinski, Britta ; Tran, Hue ; Hock, Björn ; Kolmar, Harald (2024)
Potent apoptosis induction by a novel trispecific B7-H3xCD16xTIGIT 2+1 common light chain natural killer cell engager.
In: Molecules, 29 (5)
doi: 10.3390/molecules29051140
Article, Bibliographie

This is the latest version of this item.

Abstract

Valued for their ability to rapidly kill multiple tumor cells in succession as well as their favorable safety profile, NK cells are of increasing interest in the field of immunotherapy. As their cytotoxic activity is controlled by a complex network of activating and inhibiting receptors, they offer a wide range of possible antigens to modulate their function by antibodies. In this work, we utilized our established common light chain (cLC)-based yeast surface display (YSD) screening procedure to isolate novel B7-H3 and TIGIT binding monoclonal antibodies. The chicken-derived antibodies showed single- to low-double-digit nanomolar affinities and were combined with a previously published CD16-binding Fab in a 2+1 format to generate a potent NK engaging molecule. In a straightforward, easily adjustable apoptosis assay, the construct B7-H3xCD16xTIGIT showed potent apoptosis induction in cancer cells. These results showcase the potential of the TIGIT NK checkpoint in combination with activating receptors to achieve increased cytotoxic activity.

Item Type: Article
Erschienen: 2024
Creators: Ulitzka, Michael ; Harwardt, Julia ; Lipinski, Britta ; Tran, Hue ; Hock, Björn ; Kolmar, Harald
Type of entry: Bibliographie
Title: Potent apoptosis induction by a novel trispecific B7-H3xCD16xTIGIT 2+1 common light chain natural killer cell engager
Language: English
Date: 4 March 2024
Place of Publication: Basel
Publisher: MDPI
Journal or Publication Title: Molecules
Volume of the journal: 29
Issue Number: 5
Collation: 16 Seiten
DOI: 10.3390/molecules29051140
Corresponding Links:
Abstract:

Valued for their ability to rapidly kill multiple tumor cells in succession as well as their favorable safety profile, NK cells are of increasing interest in the field of immunotherapy. As their cytotoxic activity is controlled by a complex network of activating and inhibiting receptors, they offer a wide range of possible antigens to modulate their function by antibodies. In this work, we utilized our established common light chain (cLC)-based yeast surface display (YSD) screening procedure to isolate novel B7-H3 and TIGIT binding monoclonal antibodies. The chicken-derived antibodies showed single- to low-double-digit nanomolar affinities and were combined with a previously published CD16-binding Fab in a 2+1 format to generate a potent NK engaging molecule. In a straightforward, easily adjustable apoptosis assay, the construct B7-H3xCD16xTIGIT showed potent apoptosis induction in cancer cells. These results showcase the potential of the TIGIT NK checkpoint in combination with activating receptors to achieve increased cytotoxic activity.

Uncontrolled Keywords: NK cell engager, checkpoint inhibitor, apoptosis, trispecific antibody, bispecific antibody, chicken-derived, immunotherapy, monoclonal antibodies, yeast surface display, common light chain
Identification Number: Artikel-ID: 1140
Additional Information:

This article belongs to the Section Macromolecular Chemistry

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: Interdisziplinäre Forschungsprojekte
Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
07 Department of Chemistry
07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie
07 Department of Chemistry > Clemens-Schöpf-Institut
Date Deposited: 15 May 2024 07:16
Last Modified: 15 May 2024 11:18
PPN: 518280993
Corresponding Links:
Export:
Suche nach Titel in: TUfind oder in Google

Available Versions of this Item

Send an inquiry Send an inquiry

Options (only for editors)
Show editorial Details Show editorial Details