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

• Published in: International immunopharmacology 2014-07, Vol.21 (1), p.119-127
• Main Authors: Li, Qingcui, Ren, Guiping, Xu, Liming, Wang, Qiuying, Qi, Jianying, Wang, Wenfei, Zhou, Bing, Han, Xiaohui, Sun, Cuiyu, Wu, Qiang, Yu, Yinhang, Peng, Zhongyi, Zheng, Shimin, Li, Deshan
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Bispecific - administration & dosage; Antibodies, Bispecific - genetics; Antibodies, Blocking - administration & dosage; Antibodies, Blocking - genetics; Antibody Formation - drug effects; Arthritis, Experimental - immunology; Arthritis, Experimental - therapy; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - therapy; Bispecific antibody; Bone and Bones - drug effects; Bone and Bones - pathology; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Disease Models, Animal; Down-Regulation; Humans; IL-17A; IL-1β; Interleukin-17 - immunology; Interleukin-1beta - immunology; Male; Mice; Mice, Inbred Strains; Rheumatoid arthritis (RA)
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2014.04.018

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 29days, 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. •Three bispecific and neutralizing antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1β and hIL-17A were constructed.•Three antibodies could block and neutralize IL-1β and IL-17A.•BsAB-1 appears more beneficial in treatment CIA mice than other two antibodies.