title: In situ depletion of CD4+ T cells in human skin by Zanolimumab.
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, kappa) 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.
authors.affiliation: Department of Dermatology, University of Copenhagen, Gentofte Hospital, Hellerup, Denmark. lovil01@gentoftehosp.kbhamt.dk
authors.forename: L S
authors.initials: LS
authors.lastname: Villadsen
authors.forename: L
authors.initials: L
authors.lastname: Skov
authors.forename: T N
authors.initials: TN
authors.lastname: Dam
authors.forename: F
authors.initials: F
authors.lastname: Dagnaes-Hansen
authors.forename: J
authors.initials: J
authors.lastname: Rygaard
authors.forename: J
authors.initials: J
authors.lastname: Schuurman
authors.forename: P W H I
authors.initials: PW
authors.lastname: Parren
authors.forename: J G J
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: O
authors.initials: O
authors.lastname: Baadsgaard
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy; D051379:Mice; D016513:Mice, SCID; D011565:Psoriasis / Q000188:drug therapy; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C520522:zanolimumab