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Obstacles to Anti-CD4 Therapy in Rheumatoid Arthritis

  • Joachim R Kalden
  • Harald Burkhardt
  • Hendrik Schulze-Koops
Meeting abstract
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Keywords

Placebo Rheumatoid Arthritis Clinical Benefit Clinical Efficacy Full Text 
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Full text

Monoclonal antibodies (mAbs) to CD4 have been employed in a variety of studies to patients with active rheumatoid arthritis (RA) in an attempt to control disease progression not only by preventing T cell activation but also by inducing tolerance to the putative autoantigen(s) [1,2,5]. Initial open labeled clinical trials have provided encouraging clinical results [1,2,4]. However, randomized controlled studies with chimeric immunoglobulins have largely failed to demonstrate a significant benefit of anti-CD4 mAbs over placebo [1,2,5]. Following those disappointing trials, favorable results of several dose-finding studies with high dosages of nondepleting CD4 mAbs were recently presented [1,2,6]. Whereas the mechanisms underlying the clinical benefit remain to be elucidated, it appears to be clear that depletion of CD4 T cells cannot explain clinical efficacy. Moreover, the data are consistent with the hypothesis that long lasting successful treatment of RA with mAb to CD4 might require long-term inhibition of peripheral T cell functions by non-depleting mAbs to CD4. Future studies are necessary to delineate precisely the dosing requirements for clinical benefit and to elucidate the mode of actions of anti-CD4 mAbs. Exciting new data that are indicative of a modulation of the detrimental Th1-dominated immune response in RA by anti-CD4 mAbs [6] warrant further investigation. Finally, data from animal studies suggest that new promising therapeutic perspectives in man might result from combining anti-CD4 mAbs with other biologic therapeutics [1,7,8].

References

  1. 1.
    Kalden JR, Breedveld FC, Burkhardt H, Burmester GR: Immunological treatment of autoimmune diseases. Adv Immunol . 1998, 68: 333-418.PubMedCrossRefGoogle Scholar
  2. 2.
    Schulze-Koops H, Lipsky PE: Anti-CD4 monoclonal antibody therapy in human autoimmune diseases. In Current Directions in Autoimmunity. Edited by Theofilopoulos A and Fathman CG. Basel: Karger Press. 1999,Google Scholar
  3. 3.
    Shizuru JA, Alters SE, Fathman CG: Anti-CD4 monoclonal antibodies in therapy: creation of nonclassical tolerance in the adult. Immunol Rev. 1992, 129: 105-130.PubMedCrossRefGoogle Scholar
  4. 4.
    Horneff G, Burmester GR, Emrich F, and Kalden JR: Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. Arthritis Rheum. 1991, 34: 129-140.PubMedCrossRefGoogle Scholar
  5. 5.
    van der Lubbe PA, Dijkmans BA, Markusse HM, Nassander U, Breedveld FC: A randomized, double-blind, placebo-controlled study of CD4 monoclonal antibody therapy in early rheumatoid arthritis. Arthritis Rheum. 1995, 38: 1097-1106.PubMedCrossRefGoogle Scholar
  6. 6.
    Schulze-Koops H, Davis LS, Haverty TP, Wacholtz MC, Lipsky PE: Reduction of Th1 cell activity in the peripheral circulation of patients with rheumatoid arthritis after treatment with a non-depleting humanized monoclonal antibody to CD4. J Rheumatol. 1998, 25: 2065-2076.PubMedGoogle Scholar
  7. 7.
    Wendling D, Racadot E, Toussirot E, Wijdenes J: Combination therapy of anti-CD4 and anti-IL-6 monoclonal antibodies in a case of severe spondylarthropathy. Br J Rheumatol. 1998, 35: 1330-10.1093/rheumatology/35.12.1330.CrossRefGoogle Scholar
  8. 8.
    Yin DP, Sankary HN, Chong AS, Blinder L, Ma LL, Williams JW: Effect of anti-CD4 monoclonal antibody combined with human CTLA4Ig on the survival of hamster liver and heart xenografts in Lewis rats. Transplantation. 1997, 64: 317-321. 10.1097/00007890-199707270-00024.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Ltd 2000

Authors and Affiliations

  • Joachim R Kalden
    • 1
  • Harald Burkhardt
    • 1
  • Hendrik Schulze-Koops
    • 1
  1. 1.University of Erlangen-NurembergErlangenGermany

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