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Effective inhibition of C3a-mediated pro-inflammatory response by a human C3a-specific protein binder.
- Source :
-
Biotechnology and bioengineering [Biotechnol Bioeng] 2020 Jun; Vol. 117 (6), pp. 1904-1908. Date of Electronic Publication: 2020 Mar 04. - Publication Year :
- 2020
-
Abstract
- Complement component 3a (C3a) plays a crucial role in the immune response and host defense, but it is also involved in pro-inflammatory responses, causing many inflammatory disorders. Blockade of C3a has been regarded as a potent therapeutic strategy for inflammatory diseases. Here, we present the development of a human C3a (hC3a)-specific protein binder, which effectively inhibits pro-inflammatory responses. The protein binder, which is composed of leucine-rich repeat modules, was selected against hC3a through phage display, and its binding affinity was matured up to 600 pM by further expanding the binding interface in a module-by-module manner. The developed protein binder was shown to have more than 10-fold higher specificity to hC3a compared with human C5a, exhibiting a remarkable suppression effect on pro-inflammatory response in monocyte, by blocking the interaction between hC3a and its receptor. The hC3a-specific protein binder is likely to have a therapeutic potential for C3a-mediated inflammatory diseases.<br /> (© 2020 Wiley Periodicals, Inc.)
- Subjects :
- Cells, Cultured
Complement Activation drug effects
Complement C3a immunology
Humans
Inflammation immunology
Models, Molecular
Anti-Inflammatory Agents chemistry
Anti-Inflammatory Agents pharmacology
Complement C3a antagonists & inhibitors
Inflammation drug therapy
Leucine analogs & derivatives
Leucine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0290
- Volume :
- 117
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biotechnology and bioengineering
- Publication Type :
- Academic Journal
- Accession number :
- 32068245
- Full Text :
- https://doi.org/10.1002/bit.27309