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, 2024, 29 (5)
doi: 10.26083/tuprints-00027124
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Ulitzka, Michael ; Harwardt, Julia ; Lipinski, Britta ; Tran, Hue ; Hock, Björn ; Kolmar, Harald |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Potent Apoptosis Induction by a Novel Trispecific B7-H3xCD16xTIGIT 2+1 Common Light Chain Natural Killer Cell Engager |
| Sprache: | Englisch |
| Publikationsjahr: | 14 Mai 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 4 März 2024 |
| Ort der Erstveröffentlichung: | Basel |
| Verlag: | MDPI |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Molecules |
| Jahrgang/Volume einer Zeitschrift: | 29 |
| (Heft-)Nummer: | 5 |
| Kollation: | 16 Seiten |
| DOI: | 10.26083/tuprints-00027124 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/27124 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (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. |
| Freie Schlagworte: | NK cell engager, checkpoint inhibitor, apoptosis, trispecific antibody, bispecific antibody, chicken-derived, immunotherapy, monoclonal antibodies, yeast surface display, common light chain |
| ID-Nummer: | Artikel-ID: 1140 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-271242 |
| Zusätzliche Informationen: | This article belongs to the Section Macromolecular Chemistry |
| 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): | 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: | 14 Mai 2024 14:07 |
| Letzte Änderung: | 15 Mai 2024 07:16 |
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| Suche nach Titel in: | TUfind oder in Google |
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- Potent Apoptosis Induction by a Novel Trispecific B7-H3xCD16xTIGIT 2+1 Common Light Chain Natural Killer Cell Engager. (deposited 14 Mai 2024 14:07) [Gegenwärtig angezeigt]
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