In situ depletion of CD4+ T cells in human skin by Zanolimumab.
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.
Villadsen
L S
LS
Department of Dermatology, University of Copenhagen, Gentofte Hospital, Hellerup, Denmark. lovil01@gentoftehosp.kbhamt.dk
Skov
L
L
Dam
T N
TN
Dagnaes-Hansen
F
F
Rygaard
J
J
Schuurman
J
J
Parren
P W H I
PW
van de Winkel
J G J
JG
Baadsgaard
O
O
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C520522:zanolimumab