title: A recombinant IgG-like bispecific antibody acting as interleukin-1β and interleukin-17A inhibitor exhibits a promising efficacy for rheumatoid arthritis.
abstract: Recently, targeting inflammatory cytokines in the pathogenic process of rheumatoid arthritis is now performed as a feasible biological method in therapy. However, treatments against single cytokine are often difficult to achieve the ideal therapeutic effect. Multi-target drugs permit more effective suppression of inflammation. In this study, we constructed an IgG-like bispecific antibody targeting IL-1β and IL-17A and expressed it in mammalian cells. The therapeutic efficacy was studied in CIA (collagen-induced arthritis) mice, which were administrated with either FL-BsAb1/17 (IgG-like bispecific antibody targeting IL-1β and IL-17A) or monovalent IL-1β Mab or IL-17A Mab (anti-IL-1β/IL-17A monoclonal antibody). We noticed that FL-BsAb1/17 had better effect on alleviating clinical symptom by significantly lowering arthritis score and relieving histological lesion on aspect of less damnification in synovial hyperplasia and cartilage destruction than monovalent Mab alone. In addition, FL-BsAb1/17 was more potent in inhibiting IL-1β, IL-17A, IL-6, TNF-α and anti-CCP antibody in the serum and in down-regulating the expression of IL-1β, IL-17A, IL-6, TNF-α, MMP-3 and RANKL in the spleen, compared to monovalent Mab alone. Further, the anti-inflammatory effect of FL-BsAb1/17 was demonstrated by significantly depressing Th17 cells expansion through decreasing phosphorylated STAT3 in the spleen of the CIA mice. FLS (fibroblast-like synoviocytes) from RA patients were used to examine the therapeutic efficacy of FL-BsAb1/17 in human pathological tissue. FL-BsAb1/17 could significantly decrease the production of IL-6 induced by IL-1β and/or IL-17A in FLS. In conclusion, FL-BsAb1/17 has the possibility to be a promising therapeutic agent for RA.
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Yunxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Zhihang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Guo
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Lijiao
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Song
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin 150030, China. Electronic address: deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced* / Q000628:therapy*; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells
chemical_list: D018033:Antibodies, Bispecific; D007074:Immunoglobulin G; D020381:Interleukin-17; D053583:Interleukin-1beta; D050796:STAT3 Transcription Factor
keywords: IL-17A; IL-1β; IgG-like bispecific antibody; Rheumatoid arthritis; Therapeutic efficacy