Antibody targeting of TIRC7 results in significant therapeutic effects on collagen-induced arthritis in mice

Author:

Utku N12,Heinemann T3,Winter M1,Bulwin C G2,Schlawinsky M2,Fraser P4,Nieuwenhuis E E S5,Volk H-D1,Blumberg R S5

Affiliation:

1. Institute of Medical Immunology, Charité-University of Medicine Berlin

2. xGenPat77 Pharmacogenetics AG, Berlin, Germany and Divisions of

3. Kekulé-Institute for Organic Chemistry and Biochemistry, University of Bonn, Bonn

4. Rheumatology

5. Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA

Abstract

Summary 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-α 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.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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