Anti-fractalkine antibody; Potentiality for the treatment of rheumatoid arthritis

Abstract

  Rheumatoid arthritis（RA）is an inflammatory and autoimmune disease characterized by synovitis and bone erosion. In the affected joints, synovial fibroblasts proliferation and massive infiltration of leukocytes are observed. The leukocyte infiltration into the tissues is tightly and spatiotemporally regulated by the interaction between chemokines and their receptors. Increased expression of fractalkine（FKN）and abundant infiltration of CX3CR1-expressed cells in RA joints have been reported. Therefore intervention of FKN-CX3CR1 axis could be a candidate target for RA treatment. In the collagen-induced mice arthritis model, anti-mouse fractalkine monoclonal antibody（anti-FKN mAb）showed therapeutic efficacy on synovial inflammation with the suppression of leukocytes infiltration. Furthermore, anti-FKN mAb improved the bone destruction by the direct inhibition of CX3CR1-expressed osteoclast precursors migration into the affected joints. In a Phase I clinical trial in RA patients, the humanized anti-human fractalkine monoclonal antibody（E6011）appeared to be safe and well tolerated in RA patients, and also showed effectiveness. Phase II clinical trials are in progress. In this review, we outline the contribution of FKN and CX3CR1 in RA pathogenesis and discuss the possibility for the treatment of RA by the blockade of FKN-CX3CR1 interaction.