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

  • E Montero1,

    Affiliated with

    • G Reyes2,

      Affiliated with

      • M Guibert3,

        Affiliated with

        • O Torres1,

          Affiliated with

          • N Rodriguez2,

            Affiliated with

            • J Estrada2,

              Affiliated with

              • L Torres4,

                Affiliated with

                • R Perez1,

                  Affiliated with

                  • A Hernandez2 and

                    Affiliated with

                    • A Lage1

                      Affiliated with

                      Arthritis Res20024(Suppl 1):114

                      DOI: 10.1186/ar450

                      Received: 15 January 2002

                      Published: 4 February 2002

                      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.

                      Authors’ Affiliations

                      (1)
                      Center of Molecular Immunology
                      (2)
                      Medical-Surgical Res Center
                      (3)
                      Institute of Rheumatology
                      (4)
                      Center for Clin Investigations

                      Copyright

                      © BioMed Central Ltd 2002

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