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.