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Therapeutic efficacy of three bispecific antibodies on collagen-induced arthritis mouse model

文献类型： 外文期刊

作者： Li, Qingcui 1 ; Ren, Guiping 1 ; Xu, Liming; Wang, Qiuying 1 ; Qi, Jianying 1 ; Wang, Wenfei 1 ; Zhou, Bing 1 ; Han, X 1 ;

作者机构： 1.Northeast Agr Univ, Coll Life Sci, Biopharmaceut Lab, Harbin 150030, Peoples R China

2.Key Lab Agr Biol Funct Gene, Harbin 150030, Peoples R China

3.Key Lab Agr Biol

关键词： Bispecific antibody;Rheumatoid arthritis (RA);IL-1 beta;IL-17A

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：4.932； 五年影响因子：4.624 ）

ISSN： 1567-5769

年卷期： 2014 年 21 卷 1 期

页码：

收录情况： SCI

摘要： Interleukin-1 beta (IL-1 beta) 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-1 beta 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-1 beta, 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-1 beta, IL-17A, TNF-alpha. 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. (C) 2014 Elsevier B.V. All rights reserved.

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