A bispecific antibody against IL-1β and IL-17A is beneficial for experimental rheumatoid arthritis

IL-1 beta is a pivotal cytokine and plays an important role in rheumatoid arthritis (RA). More recently, the biological therapy targeting this cytokine has been impressively effective for many RA patients, however, it remains insufficient in some patients. One of the reasons for these failures may be due to multiple cytokines involved in the disease process. In the present study, we constructed a single-chain bispecific antibody (scBsAb1/17) against both human IL-1 beta and human IL-17A which is the mediator for several key cytokines involved in the RA process such as TNF- and IL-6. A number of in vitro assays demonstrated that scBsAb1/17 simultaneously bound to both targets with a similar antigen-binding affinity as an individual single-chain antibody molecule (anti-IL-1 beta scFv or anti-IL-17A scFv). Mice with collagen-induced arthritis (CIA) were administrated with either scBsAb1/17 or individual single chain antibody alone, and we noticed that treatment with scBsAb1/17 significantly ameliorated clinical signs and alleviated histological lesion of CIA mice compared to treatments with anti-IL-1 beta scFv or anti-IL-17A scFv alone. Production of CH-specific antibodies in scBsAb1/17-treated CIA mice was substantially lower than that of single-chain antibody-treated CIA mice. In addition, scBsAb1/17 was more potent in the inhibition of collagen-specific proliferation of splenocytes and mRNA expression of TNF-, IL-6, IL-2, IL-1 beta and IFN-gamma in the spleens of CIA mice compared to a single-chain antibody alone. These results suggest that scBsAb1/17 appears more beneficial in CIA mice than monovalent single-chain antibody molecules. (C) 2012 Elsevier B.V. All rights reserved.