PloS one, 2017-09, Vol.12 (9), p.e0184278-e0184278
2017
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- Autor(en) / Beteiligte
- Titel
- A fully humanized IgG-like bispecific antibody for effective dual targeting of CXCR3 and CCR6
- Ist Teil von
- PloS one, 2017-09, Vol.12 (9), p.e0184278-e0184278
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2017
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- Chemokines and their receptors are pivotal for the trafficking of leukocytes during immune responses, and host defense. However, immune cell migration also contributes to a wide variety of autoimmune and chronic inflammatory diseases. Compelling evidence suggests that both CXCR3 and CCR6 chemokine receptors play crucial roles in the migration of pathological Th1 and Th17 cells during the course of certain inflammatory diseases. The use of two or more receptors by pathogenic cells may explain why targeting of individual receptors has proven disappointing in the clinic. We therefore hypothesized that simultaneous targeting of both CXCR3 and CCR6 with a bispecific antibody (BsAb) might result in decreased chemotaxis and/or specific depletion of pro-inflammatory T cell subsets. In this study, we designed and characterized a fully humanized BsAb. We show that the BsAb binds to both chemokine receptors, as demonstrated by Flow Cytometry and Surface Plasmon Resonance analysis. Furthermore, we demonstrate that the BsAb effectively blocks cell chemotaxis and induces specific antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. Therefore, we propose that dual targeting of CXCR3 and CCR6 with a fully humanized BsAb may display a potent interventional approach for the treatment of inflammatory and autoimmune diseases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0184278Titel-ID: cdi_plos_journals_1935803773
- Format
- –
- Schlagworte
- Alzheimer's disease, Alzheimers disease, Animals, Antibodies, Bispecific - isolation & purification, Antibodies, Bispecific - metabolism, Antibodies, Monoclonal - isolation & purification, Antibodies, Monoclonal - metabolism, Antibody-dependent cell-mediated cytotoxicity, Autoimmune diseases, Biochemistry, Biology and Life Sciences, Blood & organ donations, CCR6 protein, Cell Line, Tumor, Cell migration, Cell Movement, Chemokine receptors, Chemokines, Chemotaxis, CXCR3 protein, Cytokines, Cytometry, Cytotoxicity, Cytotoxicity, Immunologic, Dosage and administration, Flow Cytometry, Helper cells, Humans, Immune response, Immunoglobulin G, Immunoglobulin G - isolation & purification, Immunoglobulin G - metabolism, Immunoglobulins, In vitro methods and tests, Inflammatory diseases, Integrated software, Leukocyte migration, Leukocytes, Lymphocytes, Lymphocytes T, Male, Medical research, Medicine and Health Sciences, Methods, Mice, Inbred C57BL, Molecular biology, Monoclonal antibodies, Proteins, Receptors, Receptors, CCR6 - antagonists & inhibitors, Receptors, CCR6 - metabolism, Receptors, CXCR3 - antagonists & inhibitors, Receptors, CXCR3 - metabolism, Research and Analysis Methods, Rheumatoid arthritis, Surface Plasmon Resonance, T cell receptors, T cells, Toxicity