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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Smit, Martine J. Leurs, Rob Mujic-delic, Azra Saunders, Michael Verzijl, Dennis Bosch, Leontien Verrips, C. Theo Blanchetot, Christophe Rem, Louise De Haard, Hans |
| Description | Author Affiliation: Blanchetot C ( Department of Cellular Biology, Utrecht University, Utrecht, The Netherlands.) |
| Abstract | Chemokine receptors and their ligands play a prominent role in immune regulation but many have also been implicated in inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, allograft rejection after transplantation, and also in cancer metastasis. Most approaches to therapeutically target the chemokine system involve targeting of chemokine receptors with low molecular weight antagonists. Here we describe the selection and characterization of an unprecedented large and diverse panel of neutralizing Nanobodies (single domain camelid antibodies fragment) directed against several chemokines. We show that the Nanobodies directed against CCL2 (MCP-1), CCL5 (RANTES), CXCL11 (I-TAC), and CXCL12 (SDF-1 ) bind the chemokines with high affinity (at nanomolar concentration), thereby blocking receptor binding, inhibiting chemokine-induced receptor activation as well as chemotaxis. Together, we show that neutralizing Nanobodies can be selected efficiently for effective and specific therapeutic treatment against a wide range of immune and inflammatory diseases. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 35 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-08-30 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antibodies, Monoclonal Pharmacology Antibodies, Neutralizing Chemokines Metabolism Single-Domain Antibodies Animals Chemistry Genetics Immunology Camelids, New World Immune System Diseases Drug Therapy Inflammation Mice NIH 3T3 Cells Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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