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This article is part of the supplement: 22nd European Workshop for Rheumatology Research

Meeting abstract

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

E Montero1, G Reyes2, M Guibert3, O Torres1, N Rodriguez2, J Estrada2, L Torres4, R Perez1, A Hernandez2 and A Lage1

Author Affiliations

1 Center of Molecular Immunology, Havana, Cuba

2 Medical-Surgical Res Center, Havana, Cuba

3 Institute of Rheumatology, Havana, Cuba

4 Center for Clin Investigations, Havana, Cuba

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Arthritis Res 2002, 4(Suppl 1):114  doi:10.1186/ar450


The electronic version of this article is the complete one and can be found online at:


Received:15 January 2002
Published:4 February 2002

©

Meeting abstract

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.