A native-like bispecific antibody suppresses the inflammatory cytokine response by simultaneously neutralizing tumor necrosis factor-alpha and interleukin-17A
| Autor: | Ying Wang, Lili Wang, Lishan Kang, Tianshu Xu, Tianlei Ying, Liang Cheng, Liping Wang, Tao Huang, Qi Zhao, Xiaohua Douglas Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
rheumatoid arthritis Chemokine Necrosis 03 medical and health sciences Immune system medicine Immune response biology business.industry Research Paper: Immunology Immunity medicine.disease Blockade bispecific antibody IL-17 030104 developmental biology Oncology Rheumatoid arthritis TNF-α Immunology Cancer research biology.protein Immunology and Microbiology Section Tumor necrosis factor alpha Interleukin 17 medicine.symptom Antibody business Fc heterodimerization |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Anti-tumor necrosis factor (TNF) therapies are successful in the treatment of inflammatory disorders. However, some patients with rheumatoid arthritis (RA) fail to response anti-TNF drugs due to the compensation of other inflammatory signals. In this study, to reduce compensatory responses of interleukin-17A (IL-17A) during TNF-α inhibition, we generated an IgG-like bispecific antibodiy (bsAb) against TNF-α and IL-17A through a combination method of electrostatic Fc pairing and light chain crossover. This bsAb exhibited relatively high stability comparable to natural IgG antibodies, and retained the unaltered affinities to both of two targets. BsAb significantly decreased not only the expression level of neutrophil or Th17 chemokines, but also the secretion of IL-6/IL-8 on fibroblast-like synoviocytes (FLS) from a patient with RA. Meanwhile, TNF-α-mediated cellular cytotoxicity of fibroblasts was neutralized by bsAb. Importantly, we demonstrate that the combined blockade of TNF-α and IL-17A is more efficient than inhibition of either factor alone. Our results suggest the IgG-like anti-TNF-α/IL-17A bispecific molecule overcome the limited therapeutic responses using anti-TNF drugs. It may be a promising therapeutic agent for the treatment of autoimmune diseases. |
| Databáze: | OpenAIRE |
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