Pharmacological efficacy of anti-IL-1I2 scFv, Fab and full-length antibodies in treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that mainly causes the synovial joint inflammation and cartilage destruction. Interleukin-1I2 (IL-1I2) is an important proinflammatory cytokine involved in the pathogenesis of RA. In this study, we constructed and expressed anti-IL-1I2-full-length antibody in CHO-K1-SV, anti-IL-1I2-Fab and anti-IL-1I2-scFv in Rosetta. We compared the therapeutic efficacy of three anti-IL-1I2 antibodies for CIA mice. Mice with CIA were subcutaneously injected with humanized anti-IL-1I2-scFv, anti-IL-1I2-Fab or anti-IL-1I2-full-length antibody. The effects of treatment were determined by arthritis severity score, autoreactive humoral, cellular immune responses, histological lesion and cytokines production. Compared with anti-IL-1I2-scFv treatments, anti-IL-1I2-Fab and anti-IL-1I2-full-length antibody therapy resulted in more significant effect in alleviating the severity of arthritis by preventing bone damage and cartilage destruction, reducing humoral and cellular immune responses, and down-regulating the expression of IL-1I2, IL-6, IL-2, IFN-I3, TNF- alpha and MMP-3 in inflammatory tissue. The therapeutic effects of anti-IL-1I2-Fab and anti-IL-1I2-full-length antibodies on CIA mice had no significant difference. However, production of anti-IL-1I2-full-length antibody in eukaryotic system is, in general, time-consuming and more expensive than that of anti-IL-1I2-Fab in prokaryotic systems. In conclusion, as a small molecule antibody, anti-IL-1I2-Fab is an ideal candidate for RA therapy.