In situ depletion of CD4+ T cells in human skin by Zanolimumab.
Arch Dermatol Res
; 298(9): 449-55, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-17091277
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.
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Bases de datos:
MEDLINE
Asunto principal:
Piel
/
Linfocitos T CD4-Positivos
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Anticuerpos Monoclonales
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Antineoplásicos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Arch Dermatol Res
Año:
2007
Tipo del documento:
Article
País de afiliación:
Dinamarca