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Immunodiagnosis and therapeutic immunosuppression in rheumatoid arthritis with ior t1 (anti-CD6) monoclonal antibody

  • E Montero
  • G Reyes
  • M Guibert
  • O Torres
  • N Rodriguez
  • J Estrada
  • L Torres
  • R Perez
  • A Hernandez
  • A Lage
Meeting abstract

Keywords

Rheumatoid Arthritis Rheumatoid Arthritis Synovium Activate Leukocyte Cell Adhesion Molecule Cell Membrane Glycoprotein Arthritis Synovium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

CD6 antigen is a typeI cell membrane glycoprotein belonging to the scavenger receptor cysteine-rich (SRCR) superfamily groupB, predominantly expressed by T cells and a B-cell subset. CD6 binds activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily (IgSF). ALCAM is expressed on activated T cells, B cells, monocytes, skin fibroblasts, keratinocytes and rheumatoid arthritis synovium, and mediates homophilic and heterophilic adhesion. CD6-ligand interaction has been implicated in cell adhesion, T-cell maturation and regulation of activation, constituting an uncommon type of protein-protein superfamilies interaction. The ior t1 is a murine IgG2a mAb recognizing a different epitope compared to other anti-CD6 mAbs. It is in a phase II clinical trial (PIICT) for cutaneous T-cell lymphomas treatment. Recently, we reported its intravenous therapeutic effect in a Psoriasis vulgaris patient. A PIICT was performed in 18 rheumatoid arthritis patients. Technetium-99m-labeled ior t1 mAb (ior t1-99Tcm) joint uptake and body distribution was assessed by anterior and posterior whole body scans and specific regional imaging. Forty-eight hours apart started a therapeutic dose-finding study based on 7 consecutive daily doses at 0.2 mg/kg, 0.4 mg/kg or 0.8 mg/kg of iort1 mAb intravenous infusion. Clinical evaluation and laboratory analysis were performed weekly. A rapid ior t1-99Tcm/lymphocytes association and a marked radioactivity uptake form inflamed and silent joints were obtained. From biodistribution studies was estimated that more than 0.5% of the ior t1-99Tcm infusion penetrates into hands and feet with inflamed joints. iort1 joint-imaging was superior to MDP-99Tcm, used as standard method. iort1 mAb intravenous infusion induced a dose-dependent therapeutic effect. 0.4 mg/kg was defined as the Optimum Biological Dose, with a long-lasting clinical improvement observed in this group. This treatment reduced the number of tender and swollen joints starting at day 4 of the infusions. Adverse events were dose-depending but controlled by medications. It was not observed deep lymphopenia neither opportunistic infections. This is the first clinical report supporting the relevance of the CD6/CD6-ligand model as a potential target for rheumatoid arthritis immunotherapy. A PI-IICT with a humanized version for iort1 mAb is underway.

Copyright information

© BioMed Central Ltd 2002

Authors and Affiliations

  • E Montero
    • 1
  • G Reyes
    • 2
  • M Guibert
    • 3
  • O Torres
    • 1
  • N Rodriguez
    • 2
  • J Estrada
    • 2
  • L Torres
    • 4
  • R Perez
    • 1
  • A Hernandez
    • 2
  • A Lage
    • 1
  1. 1.Center of Molecular ImmunologyHavanaCuba
  2. 2.Medical-Surgical Res CenterHavanaCuba
  3. 3.Institute of RheumatologyHavanaCuba
  4. 4.Center for Clin InvestigationsHavanaCuba

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