Derm News: 2007.3(7)

In situ depletion of CD4+ T cells in human skin by Zanolimumab

Archives of Dermatological Research Volume 298, Number 9 / February, 2007 449-455
L. S. Villadsen1 , L. Skov1, T. N. Dam2, F. Dagnæs-Hansen3, J. Rygaard4, J. Schuurman5, P. W. H. I. Parren5, J. G. J. van de Winkel5, 6, 7 and O. Baadsgaard6

Abstract

CD4+ T cells, in activated or malignant form, are involved in a number of diseases including inflammatory skin diseases such as psoriasis, and T cell lymphomas such as the majority of cutaneous T cell lymphomas (CTCL). Targeting CD4 with an antibody that inhibits and/or eliminates disease-driving T cells in situ may therefore be a useful approach in the treatment of inflammatory and malignant skin diseases. Depletion of CD4+ T cells in intact inflamed human skin tissue by Zanolimumab, a fully human therapeutic monoclonal antibody (IgG1, ?) against CD4, was studied in a human psoriasis xenograft mouse model.

Zanolimumab treatment was shown to induce a significant reduction in the numbers of inflammatory mononuclear cells in upper dermis. This reduction in inflammatory mononuclear cells in situ was primarily due to a significant reduction in the numbers of skin-infiltrating CD4+, but not CD8+ CD3+ T cells. The capacity of Zanolimumab to deplete the CD4+ T cells in the skin may be of importance in diseases where CD4+ T cells play a central role.

Indeed, in a phase II clinical trial Zanolimumab has shown a dose-dependent clinical response in patients with CTCL and the antibody is currently in a phase III clinical trial for CTCL, a disease for which there is no safe and effective treatment available today.

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The Derm News service provided by the Editorial Consultants of Skin Therapy Letter^© and its founding editor Dr. Stuart Maddin.