Carrara, Stefania C. ; Bogen, Jan P. ; Fiebig, David ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald (2024)
Targeted Phagocytosis Induction for Cancer Immunotherapy via Bispecific MerTK-Engaging Antibodies.
In: International Journal of Molecular Sciences, 2022, 23 (24)
doi: 10.26083/tuprints-00027673
Artikel, Zweitveröffentlichung, Verlagsversion
 | Es ist eine neuere Version dieses Eintrags verfügbar. |
Kurzbeschreibung (Abstract)
The Tyro, Axl, and MerTK receptors (TAMRs) play a significant role in the clearance of apoptotic cells. In this work, the spotlight was set on MerTK, as it is one of the prominent TAMRs expressed on the surface of macrophages and dendritic cells. MerTK-specific antibodies were previously isolated from a transgenic rat-derived immune library with suitable biophysical properties. Further characterisation resulted in an agonistic MerTK antibody that led to phospho AKT activation in a dose-dependent manner. In this proof-of-concept study, a MerTK-specific antibody, MerK28, was combined with tandem, biparatopic EGFR-binding VHH camelid antibody domains (7D9G) in different architectures to generate bispecific antibodies with the capacity to bind EGFR and MerTK simultaneously. The bispecific molecules exhibited appropriate binding properties with regard to both targets in their soluble forms as well as to cells, which resulted in the engagement of macrophage-like THP-1 cells with epidermoid carcinoma A431 cells. Furthermore, targeted phagocytosis in co-culture experiments was observed only with the bispecific variants and not the parental MerTK-binding antibody. This work paves the way for the generation of bispecific macrophage-engaging antibodies for targeted phagocytosis harnessing the immune-modulating roles of MerTK in immunotherapy.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Carrara, Stefania C. ; Bogen, Jan P. ; Fiebig, David ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Targeted Phagocytosis Induction for Cancer Immunotherapy via Bispecific MerTK-Engaging Antibodies |
| Sprache: | Englisch |
| Publikationsjahr: | 19 August 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2022 |
| Ort der Erstveröffentlichung: | Basel |
| Verlag: | MDPI |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | International Journal of Molecular Sciences |
| Jahrgang/Volume einer Zeitschrift: | 23 |
| (Heft-)Nummer: | 24 |
| Kollation: | 17 Seiten |
| DOI: | 10.26083/tuprints-00027673 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/27673 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichungsservice |
| Kurzbeschreibung (Abstract): | The Tyro, Axl, and MerTK receptors (TAMRs) play a significant role in the clearance of apoptotic cells. In this work, the spotlight was set on MerTK, as it is one of the prominent TAMRs expressed on the surface of macrophages and dendritic cells. MerTK-specific antibodies were previously isolated from a transgenic rat-derived immune library with suitable biophysical properties. Further characterisation resulted in an agonistic MerTK antibody that led to phospho AKT activation in a dose-dependent manner. In this proof-of-concept study, a MerTK-specific antibody, MerK28, was combined with tandem, biparatopic EGFR-binding VHH camelid antibody domains (7D9G) in different architectures to generate bispecific antibodies with the capacity to bind EGFR and MerTK simultaneously. The bispecific molecules exhibited appropriate binding properties with regard to both targets in their soluble forms as well as to cells, which resulted in the engagement of macrophage-like THP-1 cells with epidermoid carcinoma A431 cells. Furthermore, targeted phagocytosis in co-culture experiments was observed only with the bispecific variants and not the parental MerTK-binding antibody. This work paves the way for the generation of bispecific macrophage-engaging antibodies for targeted phagocytosis harnessing the immune-modulating roles of MerTK in immunotherapy. |
| Freie Schlagworte: | macrophages, targeted phagocytosis, MerTK, EGFR, bispecific antibody, BiME |
| ID-Nummer: | Artikel-ID: 15673 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-276735 |
| 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: | 19 Aug 2024 09:56 |
| Letzte Änderung: | 20 Aug 2024 06:20 |
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| Suche nach Titel in: | TUfind oder in Google |
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- Targeted Phagocytosis Induction for Cancer Immunotherapy via Bispecific MerTK-Engaging Antibodies. (deposited 19 Aug 2024 09:56) [Gegenwärtig angezeigt]
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