In situ depletion of CD4+ T cells in human skin by Zanolimumab |
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Authors: | L. S. Villadsen L. Skov T. N. Dam F. Dagnæs-Hansen J. Rygaard J. Schuurman P. W. H. I. Parren J. G. J. van de Winkel O. Baadsgaard |
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Affiliation: | (1) Department of Dermatology, University of Copenhagen, Gentofte Hospital, Hellerup, Denmark;(2) Department of Dermatology, Roskilde Hospital, Roskilde, Denmark;(3) Department of Medical Microbiology, University of Aarhus, Aarhus, Denmark;(4) Bartholin Institute, University Hospital of Copenhagen, Copenhagen, Denmark;(5) Genmab B.V., Utrecht, The Netherlands;(6) Genmab A/S, Copenhagen, Denmark;(7) Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands |
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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, κ) 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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Keywords: | Human CD4 antibodies Psoriasis CTCL Inflammatory skin diseases Xenograft model |
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