Skip to main content


Candidate targets for antibody therapy of rheumatoid arthritis: CD64 and IL-15

At present, blockade of cytokines represents one approach to treat rheumatoid arthritis (RA). Anti-tumor necrosis factor (TNF)-α therapy results in impressive protection against joint inflammation and joint damage in RA patients, although a significant number of patients do not respond. We evaluated blockade of targets more upstream in the inflammation cascade, of activated macrophages and of IL-15.

Inflammatory macrophages exhibit enhanced expression of FcγRI (CD64), the high-affinity receptor for IgG. We observed the presence of CD64 on activated macrophages in RA patients, and their in vitro elimination using a CD64-targed immunotoxin. In addition, we demonstrated in vivo elimination of CD64-expressing activated macrophages, resulting in significant inhibition of disease activity in an adjuvant arthritis model, in newly generated human CD64 transgenic rats. IL-15 triggers inflammatory cell recruitment, angiogenesis and production of other inflammatory cytokines, including IFN-γ, TNF-α and IL-17, which are all upregulated in inflammation. We generated monoclonal antibodies using human immunoglobulin-transgenic mice. One of the IL-15-specific antibodies, HuMax IL-15, did not compete with IL-15 for binding to its receptor, but potently interfered with the assembly of the IL-15 receptor α,β,γ complex. This antibody blocked IL-15-induced T-cell proliferation, and monocyte TNF-α release in vitro. HuMax IL-15 effectively inhibited inflammation in SCID-RA models and is currently clinically evaluated in human RA.

Author information

Rights and permissions

Reprints and Permissions

About this article


  • Rheumatoid Arthritis
  • Rheumatoid Arthritis Patient
  • Human CD64
  • Joint Damage
  • Joint Inflammation