1. Antibody targeting of TIRC7 results in significant therapeutic effects on collagen-induced arthritis in mice.
- Author
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Utku N, Heinemann T, Winter M, Bulwin CG, Schlawinsky M, Fraser P, Nieuwenhuis EE, Volk HD, and Blumberg RS
- Subjects
- Animals, Arthritis, Experimental therapy, Arthritis, Rheumatoid immunology, Arthritis, Rheumatoid therapy, B-Lymphocytes immunology, Female, Humans, Immunoglobulin G immunology, Immunologic Memory immunology, Immunotherapy methods, Knee Joint immunology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred DBA, Receptors, Tumor Necrosis Factor immunology, Synovial Fluid immunology, T-Lymphocytes immunology, Tumor Necrosis Factor-alpha immunology, Up-Regulation immunology, Antibodies, Monoclonal immunology, Arthritis, Experimental immunology, Vacuolar Proton-Translocating ATPases immunology
- Abstract
TIRC7 is a cell surface molecule which is expressed in T and B lymphocytes and negatively regulates their function. Anti-TIRC7 specific monoclonal antibody (mAb) inhibited T cell memory response to recall antigens. Up-regulation of TIRC7 on lymphocytes from joint tissue of patients with Rheumatoid Arthritis (RA) and mice with collagen induced arthritis (CIA) suggested TIRC7 as a novel target to promote anti-inflammatory reaction. Anti-TIRC7 mAb administration significantly inhibited the induction and progression of CIA and the anti-collagen IgG1 and IgG2a antibody response. Combination therapy of anti-TIRC7 mAb and soluble TNF-alpha receptor demonstrated an increased inhibitory effect over the single compounds on CIA. The results demonstrate the therapeutic potential of TIRC7 targeting with mAb in diseases associated with exaggerated T and B cell responses.
- Published
- 2006
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