Antibody-based delivery of IL4 to the neovasculature cures mice with arthritis

Significance Disease-homing antibody–cytokine fusion proteins (immunocytokines) are considered as innovative biopharmaceutical agents for the therapy of cancer and chronic inflammatory conditions with the potential to modulate the activity of the immune system at the site of disease. The immunocytokine F8-IL4 was able to selectively localize to arthritic sites in vivo and exhibited a potent single-agent activity in the collagen-induced arthritis model in mice. Surprisingly, the combination treatment of F8-IL4 with dexamethasone cured 100% of treated mice with established arthritis. To our knowledge, this is the first report of durable and complete regressions in mice with established RA. These findings are of clinical significance as the F8 antibody recognizes its cognate antigen, the extra domain A of fibronectin, with comparable affinity in mouse and man.