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A native-like bispecific antibody suppresses the inflammatory cytokine response by simultaneously neutralizing tumor necrosis factor-alpha and interleukin-17A
Xu, Tianshu1; Ying, Tianlei2; Wang, Lili2; Zhang, Xiaohua Douglas3; Wang, Ying4; Kang, Lishan5; Huang, Tao5; Cheng, Liang5; Wang, Liping1; Zhao, Qi3
2017-10-10
Source PublicationONCOTARGET
ISSN1949-2553
Volume8Issue:47Pages:81860-81872
Abstract

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-alpha inhibition, we generated an IgG-like bispecific antibodiy (bsAb) against TNF-alpha 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-alpha-mediated cellular cytotoxicity of fibroblasts was neutralized by bsAb. Importantly, we demonstrate that the combined blockade of TNF-alpha and IL-17A is more efficient than inhibition of either factor alone. Our results suggest the IgG-like anti-TNF-alpha/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.

KeywordBispecific Antibody Fc Heterodimerization Tnf-alpha Il-17 Rheumatoid Arthritis Immunology And Microbiology Section Immune Response Immunity
DOI10.18632/oncotarget.19899
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000412683900020
PublisherIMPACT JOURNALS LLC
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:9   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Institute of Chinese Medical Sciences
Corresponding AuthorWang, Liping; Zhao, Qi
Affiliation1.School of Life Science, Jilin University, Changchun, Jilin, China
2.School of Basic Medical Sciences, Fudan University, Shanghai, China
3.Faculty of Health Sciences, University of Macau, Taipa, Macau, China
4.Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China
5.Novo Nordisk Research Centre China, Beijing, China
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Xu, Tianshu,Ying, Tianlei,Wang, Lili,et al. A native-like bispecific antibody suppresses the inflammatory cytokine response by simultaneously neutralizing tumor necrosis factor-alpha and interleukin-17A[J]. ONCOTARGET,2017,8(47):81860-81872.
APA Xu, Tianshu.,Ying, Tianlei.,Wang, Lili.,Zhang, Xiaohua Douglas.,Wang, Ying.,...&Zhao, Qi.(2017).A native-like bispecific antibody suppresses the inflammatory cytokine response by simultaneously neutralizing tumor necrosis factor-alpha and interleukin-17A.ONCOTARGET,8(47),81860-81872.
MLA Xu, Tianshu,et al."A native-like bispecific antibody suppresses the inflammatory cytokine response by simultaneously neutralizing tumor necrosis factor-alpha and interleukin-17A".ONCOTARGET 8.47(2017):81860-81872.
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