Development and use of alefacept to treat psoriasis

Krueger, Gerald G.; Callis, Kristina P.

doi:10.1016/mjd.2003.552

Cited by 97 publications

(73 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Demographics are shown in supplementary Table A. 4 They were treated with 15 mg Alefacept i.m. weekly.…”

Section: Design Of Psoriasis Studymentioning

confidence: 99%

“…The disease manifests with marked infiltration of T lymphocytes, dendritic cells, and neutrophils in the skin and hyperplasia of the epidermis. An approved drug for treatment of psoriasis is Alefacept, a fully human protein composed of the extracellular portion of lymphocyte-function-associated Ag type 3 (LFA-3 or CD58) and the Fc domain of IgG1 (ϭ LFA3TIP) (1)(2)(3)(4)(5)(6)(7)(8)(9). Its supposed action is based on inhibition of costimulation via blocking CD2 and granzyme-induced apoptosis due to Fc␥R III binding (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Expression of Tolerance Associated Gene-1, a Mitochondrial Protein Inhibiting T Cell Activation, Can Be Used to Predict Response to Immune Modulating Therapies

Keeren

Friedrich

Gebuhr

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Immune modulating therapies gain increasing importance in treatment of patients with autoimmune diseases such as psoriasis. None of the currently applied biologics achieves significant clinical improvement in all treated patients. Because the therapy with biologics is cost intensive and sometimes associated with side effects, noninvasive diagnostic tools for early prediction of responders are of major interest. We studied the effects of Alefacept (LFA3Ig), an approved drug for treatment of psoriasis, on leukocytes in vitro and in vivo to identify gene markers predictive for treatment response and to further investigate its molecular mechanisms of action. In an open-label study, 20 psoriasis patients were treated weekly with 15 mg Alefacept over 12 wk. We demonstrate that transcription of the tolerance-associated gene (TOAG-1) is significantly up-regulated whereas receptor for hyaluronic acid mediated migration (RHAMM) transcription is down-regulated in PBMCs of responding patients before clinical improvement. TOAG-1 is exclusively localized within mitochondria. Overexpression of TOAG-1 in murine T cells leads to increased susceptibility to apoptosis. Addition of Alefacept to stimulated human T cells in vitro resulted in reduced frequencies of activated CD137+ cells, increased TOAG-1 but reduced RHAMM expression. This was accompanied by reduced proliferation and enhanced apoptosis. Inhibition of proliferation was dependent on enhanced PDL1 expression of APCs. Thus, peripheral changes of TOAG-1 and RHAMM expression can be used to predict clinical response to Alefacept treatment in psoriasis patients. In the presence of APCs Alefacept can inhibit T cell activation and survival by increasing expression of TOAG-1 on T cells and PDL1 on APCs.

show abstract

“…Demographics are shown in supplementary Table A. 4 They were treated with 15 mg Alefacept i.m. weekly.…”

Section: Design Of Psoriasis Studymentioning

confidence: 99%

mentioning

confidence: 99%

Expression of Tolerance Associated Gene-1, a Mitochondrial Protein Inhibiting T Cell Activation, Can Be Used to Predict Response to Immune Modulating Therapies

Keeren

Friedrich

Gebuhr

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…No relationship has been observed between the decrease in lymphocyte count and the incidence of cutaneous malignancies or infections in treated patients [40]. No reportsof disease rebound or flare on discontinuation of therapy after the first 12 weeks of treatment have been reported [41].…”

Section: Alefaceptmentioning

confidence: 99%

Cutaneous Adverse Events of Biological Therapy for Psoriasis: Review of the Literature

Thielen¹,

Kuenzli²,

Saurat³

2005

Dermatology

View full text Add to dashboard Cite

The use of biological agents is expanding worldwide as a new treatment alternative for chronic inflammatory diseases including more recently skin diseases, especially psoriasis. Although frequently observed, the knowledge about acute and chronic dermatological adverse events is limited, and potential pathogenic mechanisms still have to be identified. Exact diagnosis is required considering that dermatological adverse events raise a decisional challenge about potential treatment discontinuation. The object of this publication is to present an overview of the dermatological adverse events of these new treatment alternatives.

show abstract

“…The large pivotal clinical trials reveal Introduction Alefacept is a recombinant human leukocyte function antigen (LFA) 3/immunoglobulin G1 fusion protein that is being designed to prevent the interaction between LFA-3 and CD2 [1] . Additionally, the protein is able to induce apoptosis in critical subgroups of T cells (CD45RO+ memory T cells) by engaging Fc ␥ RI and Fc ␥ RIII immunoglobulin receptors [2] . Alefacept has been approved by the FDA for treatment of moderate to severe chronic plaque psoriasis in the USA and very recently also in Israel and Switzerland.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Remission after 1 Course of 12 Weeks of Alefacept Therapy – A Case Report

Vitéz¹,

Heese²,

Wozel³

2005

Dermatology

View full text Add to dashboard Cite

Development and use of alefacept to treat psoriasis

Cited by 97 publications

References 12 publications

Expression of Tolerance Associated Gene-1, a Mitochondrial Protein Inhibiting T Cell Activation, Can Be Used to Predict Response to Immune Modulating Therapies

Expression of Tolerance Associated Gene-1, a Mitochondrial Protein Inhibiting T Cell Activation, Can Be Used to Predict Response to Immune Modulating Therapies

Cutaneous Adverse Events of Biological Therapy for Psoriasis: Review of the Literature

Long-Term Remission after 1 Course of 12 Weeks of Alefacept Therapy – A Case Report

Contact Info

Product

Resources

About