In a preliminary clinical trial, an antibody binding to CD2 (siplizumab), which was expressed on memory effector T-lymphocytes, was successfully evaluated in psoriasis (Bayes et al., 2003). An antibody directed against CD3 (visilizumab), a component of the T-cell receptor complex, which is expressed on all T-lymphocytes, is currently investigated for its efficacy in graft-versus-host disease and previously has been reported to have some therapeutic activity in psoriasis but may not be further developed for this indication (Carpenter et al., 2005). Several antibodies have been constructed against CD4 expressed on T-cells. According to the first clinical trials, HuMax-CD4 and OKT(R)cdr4a appear to be effective in the treatment of psoriasis (Bachelez et al., 1998; Gniadecki et al., 2002; Skov et al., 2003; Barry and Kirby, 2004).
Since T-helper cells may contribute directly to cutaneous tissue damage in LE by stimulating both macrophages and cytotoxic, specific inhibition of the T-helper cells using anti-CD4 was considered as a suitable approach to suppress disease activity (Owen and Harrison, 2000). Therefore, a recombinant chimeric CD4 monoclonal antibody (cM-T412) was investigated in clinical trials for its efficacy in the treatment of LE (Prinz et al., 1996). Treatment of five patients with chronic discoid LE including two patients with systemic involvement resulted in an immediate improvement in the skin lesions. Moreover, proteinuria as an index of lupus nephropathy was fully resolved and the antibody was well tolerated. Further controlled clinical trials are required to prove these very promising though preliminary results.
Antibodies against the interleukin (IL)-2Ra chain (daclizumab, basiliximab, and inolimomab), antibodies against T-cell markers and IL-2/toxin fusion proteins are currently investigated in many T-cell mediated diseases. According to clinical studies, there is some evidence of the efficacy of anti-IL-2 in the treatment of psoriasis (Owen and Harrison, 2000; Mrowietz et al., 2000; Krueger et al., 2000). Recently, in a patient with severe chronic atopic dermatitis, the successful use of basiliximab, a chimeric anti-IL-2 receptor monoclonal antibody, has been reported (Kagi & Heyer, 2001). DAB389IL-2 is an IL-2 receptor specific fusion protein in which the receptor-binding domain of the diphtheria toxin has been replaced by human IL-2 and the membrane translocating and cytotoxic domains have been retained. Clinical and laboratory investigations have demonstrated a selective destruction of IL-2 receptor expressing T-lymphocytes and DAB389IL-2 has been successfully used in clinical trials for the treatment of cutaneous T-cell lymphomas and psoriasis. The most common side effects observed were flu-like symptoms with severity increasing at higher doses (Bagel et al., 1998; Martin et al., 2001; Eklund and Kuzel, 2005). Experimental approaches with immuno-cytokines being fusion proteins of IL-2 with tumour antigens have yielded promising results in the treatment of melanoma and lymphoma (Davis and Gillies, 2003; Gillies et al., 2005).
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Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.