Selective targeting of T cell subsets: focus on alefacept - a remittive therapy for psoriasis.
Psoriasis is an immune-mediated disease in which memory-effector (CD45RO+), skin-homing T cells play a key role in driving the disease process. Available therapies are often poorly tolerated, none are curative and most only suppress disease symptoms without attacking the underlying cause of the illness. Alefacept (Ameviv, Biogen, Inc.) is a fully human lymphocyte function associated antigen-3/immunoglobulin G1 fusion protein that targets memory-effector T cells by binding CD2 on the T cell and Fc phi receptor III IgG receptors on accessory cells, thereby preventing T cell activation and proliferation and causing selective T cell apoptosis. To date, alefacept has been studied in moderate-to-severe chronic plaque psoriasis and in a pilot study of psoriatic arthritis. In chronic plaque psoriasis, alefacept produced significant and sustained improvements in psoriasis symptoms. There was no evidence of disease rebound or worsening of psoriasis following treatment cessation. Multiple courses provided consistent efficacy, with a trend for more rapid and greater clinical improvement in subsequent courses. Alefacept reduced circulating CD4+ and CD8+ memory-effector T cells, with relatively no change in naive (CD45RA+) T cells or B cells. Alefacept also reduced IFN-phi-secreting Tcells in lesional biopsies of psoriatic skin. These reductions all correlated with the observed clinical effect. Alefacept was well-tolerated throughout these studies, with a side effect profile similar to placebo. There was no evidence of generalised immunosuppression or increased risk of infection or malignancy. Alefacept did not alter the primary or acquired immune response in psoriatic patients. Clinical data obtained to date support the use of alefacept as a safe and remittive therapy for psoriasis.
Krueger
Gerald G
GG
Department of Dermatology, University of Utah Health Sciences Center, 50 N. Medical Drive, Suite 4B 454, Salt Lake City, UT 84132, USA. krueger@ultraderm.med.utah.edu
D000077944:Alefacept; D000818:Animals; D002986:Clinical Trials as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D018655:Lymphocyte Count; D011565:Psoriasis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D011993:Recombinant Fusion Proteins; D000077944:Alefacept