Monoclonal Antibodies and Fusion Proteins

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Various inflammatory parameters have been shown or suspected to be involved in the pathogenesis of LE, including humoral factors like cytokines or soluble cytokine receptors and cellular proteins like adhesion molecules, receptors, and the various participants of the T-cell receptor-mediated activation. A variety of monoclonal antibodies have become available within the past few years and are used in human disease, including phase I and II studies on SLE. They specifically target these proteins and may modulate inflammatory disease activity (Gelfand 2001, Isaacs 2001).

Blockage of co-stimulatory molecules has been accomplished by anti-CTLA4 immunoglobulin and anti-CD40 ligand. Their clinical effectiveness has been described within the context of systemic disease; effects on concomitant skin rash, however, have been reported. B-cell depletion parallel to improvement in rash, arthritis, and fatigue has been described for anti-CD20 antibody. Promising results have been found with anti-IL-8 antibodies as well as other anticytokine antibodies like anti-IL-10. Excellent reviews on treatment options with biologicals are given by Gescuk and Davis (Gescuk and Davis 2002), Isenberg and Leckie (Isenberg and Leckie 2002), and Watts (Watts 2000).

Refractory CLE has been successfully treated with chimeric monoclonal anti-CD4 antibody infusion in five patients with long-lasting remission and has regained responsiveness to conventional treatment (Prinz et al. 1996).

The therapeutic responses mediated by thalidomide are explained by modulation of TNF-a and suggest positive results by other strategies targeting this cytokine. Therefore, monoclonal anti-TNF-a antibody (infliximab) (Gescuk and Davis 2002, Pisetksky 2000) or soluble TNF-a receptor (etanercept) (DeBrandt et al. 2001), who, however, describe induction of SLE by this fusion proteins during treatment of rheumatoid arthritis) may play an important role in the treatment of LE in the future, including its cutaneous manifestations, and will have to be evaluated in future studies. However, propagation of infections as well as long-term side effects like induction of tumors or other autoimmune diseases will have to be evaluated (DeBrandt et al. 2001, Isenberg and Leckie 2002, Watts 2000).

In summary, in SLE, a variety of different biologicals have been applied with grossly diverging results. Targeting single, pathogenetically relevant parameters by monoclonal antibodies or receptor proteins is partly disappointing in clinical practice when moderate efficacy or unforeseen side effects are encountered. At this stage, any of these approaches are restricted to refractory or severely organ-threatening SLE and have not been specifically applied to CLE.

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  • frank
    Do fusion proteins act as antibodies?
    2 years ago

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