Antibody targeting of TIRC7 results in significant therapeutic effects on collagen-induced arthritis in mice.
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.
Utku
N
N
Institute of Medical Immunology, Charité-University of Medicine Berlin, Germany. nalan.utku@charite.de
Heinemann
T
T
Winter
M
M
Bulwin
C G
CG
Schlawinsky
M
M
Fraser
P
P
Nieuwenhuis
E E S
EE
Volk
H-D
HD
Blumberg
R S
RS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D007719:Knee Joint / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D025262:Vacuolar Proton-Translocating ATPases / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; C472421:TCIRG1 protein, human; D014409:Tumor Necrosis Factor-alpha; D025262:Vacuolar Proton-Translocating ATPases