TNFRSF receptor-specific antibody fusion proteins with targeting controlled FcγR-independent agonistic activity
Please always quote using this URN: urn:nbn:de:bvb:20-opus-223948
- Antibodies specific for TNFRSF receptors that bind soluble ligands without getting properly activated generally act as strong agonists upon FcγR binding. Systematic analyses revealed that the FcγR dependency of such antibodies to act as potent agonists is largely independent from isotype, FcγR type, and of the epitope recognized. This suggests that the sole cellular attachment, achieved by Fc domain-FcγR interaction, dominantly determines the agonistic activity of antibodies recognizing TNFRSF receptors poorly responsive to soluble ligands. InAntibodies specific for TNFRSF receptors that bind soluble ligands without getting properly activated generally act as strong agonists upon FcγR binding. Systematic analyses revealed that the FcγR dependency of such antibodies to act as potent agonists is largely independent from isotype, FcγR type, and of the epitope recognized. This suggests that the sole cellular attachment, achieved by Fc domain-FcγR interaction, dominantly determines the agonistic activity of antibodies recognizing TNFRSF receptors poorly responsive to soluble ligands. In accordance with this hypothesis, we demonstrated that antibody fusion proteins harboring domains allowing FcγR-independent cell surface anchoring also act as strong agonist provided they have access to their target. This finding defines a general possibility to generate anti-TNFRSF receptor antibodies with FcγR-independent agonism. Moreover, anti-TNFRSF receptor antibody fusion proteins with an anchoring domain promise superior applicability to conventional systemically active agonists when an anchoring target with localized disease associated expression can be addressed.…
Author: | Juliane Medler, Johannes Nelke, Daniela Weisenberger, Tim Steinfatt, Moritz Rothaug, Susanne Berr, Thomas Hünig, Andreas Beilhack, Harald Wajant |
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URN: | urn:nbn:de:bvb:20-opus-223948 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Virologie und Immunbiologie |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Language: | English |
Parent Title (English): | Cell Death & Disease |
Year of Completion: | 2019 |
Volume: | 10 |
Article Number: | 224 |
Source: | Cell Death & Disease (2019) 10:224. https://doi.org/10.1038/s41419-019-1456-x |
DOI: | https://doi.org/10.1038/s41419-019-1456-x |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | biologics; proteins |
Release Date: | 2024/07/11 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |