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 

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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