Development of an AffiMab Engineered to Simultaneously Target IL-6 and TNF for Therapeutic Use in Rheumatoid Arthritis

摘要

Antibodies may be functionalized using Affibody Molecules to create bispecific AffiMabs. We used protein engineering to develop single-construct biologics suitable for blocking inflammation driven by a combination of cytokines. Ada-ZIL-6 is an AffiMab simultaneously targeting interleukin 6 (IL-6) and the tumor necrosis factor (TNF). From a set of IL-6-binding Affibody molecules selected by phage display, one variant, ZIL-6_13 with an affinity (KD) for IL-6 of 200 pM, showed the best performance of blocking the interaction between complexes of soluble IL-6 receptor (sIL-6RD) and IL-6 and the co-receptor gp130 (IL-6 trans signaling pathways).