Ann Rheum Dis 64:865-870 doi:10.1136/ard.2004.028845
  • Extended report

Depletion of synovial macrophages in rheumatoid arthritis by an anti-FcγRI-calicheamicin immunoconjugate

  1. J A G van Roon1,2,
  2. J W J Bijlsma1,
  3. J G J van de Winkel2,3,
  4. F P J G Lafeber1
  1. 1Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, PO Box 85500, 3508 GA, The Netherlands
  2. 2Immunotherapy Laboratory, Department of Immunology, University Medical Centre Utrecht, PO Box 85500, 3508 GA, The Netherlands
  3. 3Genmab, Utrecht, The Netherlands
  1. Correspondence to:
    Dr J A G van Roon
    Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, F02.127, Utrecht, PO Box 85500, 3508 GA, The Netherlands;
  • Accepted 9 October 2004
  • Published Online First 11 November 2004


Background: Monocytes/macrophages have an important and versatile role in joint inflammation and destruction in rheumatoid arthritis (RA).

Objective: To determine the efficiency of monocyte/macrophage elimination by a new drug conjugated antibody (CD64-calicheamicin (CD64-CaMi)) directed to the high affinity receptor for IgG (FcγRI).

Methods: Mononuclear cells from peripheral blood and synovial fluid of patients with RA were cultured in the presence of CD64-CaMi. Cell death of monocytes/macrophages was measured by analysis of phenotypic changes (light scatter patterns, CD14 expression, and FcγRI expression) and nuclear DNA fragmentation. The selectivity of CD64-CaMi was checked by using FcγRI deficient and FcγRI transfected cell lines. In addition, the indirect effect of CD64-CaMi-induced macrophage cell death on arthritogenic T(h1) cell activity was determined.

Results: Inflammatory macrophages from RA synovial fluid, expressing increased FcγRI levels, were efficiently killed by CD64-CaMi through induction of DNA fragmentation. CD64-CaMi-induced cell death of monocytes/macrophages from peripheral blood of patients with RA proved less efficient. Induction of synovial macrophage death by CD64-CaMi was accompanied by efficient inhibition of proinflammatory T(h1) cytokine production.

Conclusion: Together, the presented data suggest that elimination of macrophages through a new FcγRI directed CD64-CaMi is feasible. Because monocytes from peripheral blood are also eliminated by this immunoconjugate, additional experimental studies should validate its potential for local (intra-articular) application in the treatment of RA.