Fan K et al. (2008) Treatment of collagen-induced arthritis with an anti-osteopontin monoclonal antibody through promotion of apoptosis of both murine and human activated T cells. Arthritis Rheum 58: 2041–2052

Previous studies have demonstrated that osteopontin, a proinflammatory cytokine, has an important role in the pathogenesis of rheumatoid arthritis (RA). To exploit osteopontin as a potential therapeutic target, Fan et al. examined the efficacy of two novel anti-osteopontin monoclonal antibodies (mAbs; 23C3 and F8E11) in the treatment of murine collagen-induced arthritis (CIA), an animal model of human RA.

CIA was induced in DBA/1J mice by administration of two doses of type II collagen, 21 days apart. The mice were treated with anti-osteopontin mAb or control IgG, either from the time of the first immunization (control group), or after the second immunization (established CIA treatment group). Both mAbs were effective in inhibiting the development of CIA, whereas reversal of established disease was only achieved with mAb 23C3. Osteopontin was observed to prevent apoptosis of type II collagen-activated T cells and of T cells in the synovial fluid of patients with RA. On addition of mAb 23C3, T-cell apoptosis was drastically increased. The authors identified the epitope ATWLNPDPSQKQ (the binding site for mAb 23C3) within osteopontin as being directly involved in protection of activated T cells.

According to Fan and colleagues, the ability of mAb 23C3 to promote apoptosis of activated T cells indicates that the mAb could provide a new treatment option for RA.