title: Therapeutic efficacy of three bispecific antibodies on collagen-induced arthritis mouse model.
abstract: Interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are inducible factors and important cytokines in the pathogenesis of rheumatoid arthritis (RA). In the present study, three bispecific and neutralizing antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1β and hIL-17A were constructed, their therapeutic efficacy was compared on collagen induced arthritis (CIA) model mice. In vitro assays demonstrated that the three antibodies could simultaneously bind to target both hIL-1β and hIL-17A. Mice with CIA were subcutaneously administered with one of three antibodies every two days for 29 days, we noticed that, compared with the BsAB-2 and BsAB-3, BsAB-1 antibody therapy resulted in more significant effect on alleviating the severity of arthritis by preventing bone damage and cartilage destruction and substantially decreasing production of CII-specific antibodies. In addition, BsAB-1 antibody was more potent in the inhibition of mRNA expression of IL-2, IL-1β, IL-17A, TNF-α and MMP-3 in the spleen of CIA mice compared to the other two. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 for the treatment of RA model mice, and may be chosen as an ideal candidate for further development of therapeutic drugs for treatment of RA.
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Qingcui
authors.initials: Q
authors.lastname: Li
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China; Key Laboratory of agricultural biological function gene, 150030, Harbin, China.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: Heilongjiang River Fishery Research Institute, Chinese Academy of Fishery Sciences, 150070, Harbin, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Xu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Qiuying
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Qi
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Han
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Cuiyu
authors.initials: C
authors.lastname: Sun
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Yinhang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Hospital of Heilongjiang Province, Harbin, 150030, Harbin, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Peng
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 150030, Harbin, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030, Harbin, China; Key Laboratory of agricultural biological function gene, 150030, Harbin, China. Electronic address: deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000235:genetics; D019138:Antibodies, Blocking / Q000008:administration & dosage* / Q000235:genetics; D000917:Antibody Formation / Q000187:drug effects; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D018033:Antibodies, Bispecific; D019138:Antibodies, Blocking; D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta
keywords: Bispecific antibody; IL-17A; IL-1β; Rheumatoid arthritis (RA)