Administration of DAB389IL-2 to patients with recalcitrant psoriasis: A double-blind, phase II multicenter trial

Bagel, Jerry; Garland, W. Thomas; Breneman, Debra; Holick, Michael F.; Littlejohn, Thomas; Crosby, David J.; Faust, Holly B.; Fivenson, David P.; Nichols, Jean

doi:10.1016/s0190-9622(98)70590-0

Cited by 91 publications

(34 citation statements)

References 11 publications

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“…They have also constructed an IL-2 version of the diphtheria toxinbased fusion toxin, DAB-IL-2, and applied this to the treatment of cutaneous T cell lymphoma (25). Preliminary studies using DAB-IL-2 for the treatment of severe rheumatoid arthritis and severe methotrexate-resistant psoriasis have also been reported (26,27). Therefore, DAB389 IL-7 may be promising in the treatment of disorders other than hematological malignancies.…”

Section: Discussionmentioning

confidence: 99%

Mucosal T Cells Expressing High Levels of IL-7 Receptor Are Potential Targets for Treatment of Chronic Colitis

Yamazaki

Yajima²,

Tanabe

et al. 2003

The Journal of Immunology

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The IL-7/IL-7R-dependent signaling pathway plays a crucial role in regulating the immune response in intestinal mucosa. Here we demonstrate the pivotal role of this pathway in the development and treatment of chronic colitis. T cells expressing high levels of IL-7R were substantially infiltrated in the chronic inflamed mucosa of TCR α-chain knockout mice and IL-7 transgenic mice. Transfer of mucosal T cells expressing high levels of IL-7R, but not T cells expressing low levels of IL-7R, from these mice into recombinase-activating gene-2−/− mice induced chronic colitis. Selective elimination of T cells expressing high levels of IL-7R by administrating small amounts of toxin-conjugated anti-IL-7R Ab completely ameliorated established, ongoing colitis. These findings provide evidence that therapeutic approaches targeting mucosal T cells expressing high levels of IL-7R are effective in the treatment of chronic intestinal inflammation and may be feasible for use in the therapy of human inflammatory bowel disease.

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Section: Discussionmentioning

confidence: 99%

Mucosal T Cells Expressing High Levels of IL-7 Receptor Are Potential Targets for Treatment of Chronic Colitis

Yamazaki

Yajima²,

Tanabe

et al. 2003

The Journal of Immunology

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“…The efficacy of alefacept [a fusion protein targeting leukocyte functioning antigen-3, LFA-3, which induces apoptosis of memory effector (activated) T cells in psoriasis] and efaluzimab (a monoclonal antibody to LFA-1), which also targets memory T cells in psoriasis, substantiate the view that T cells may have a primary pathogenic role [8,9] . In addition, the efficacy of the fusion protein DAB 389-IL-2 (comprising IL-2 and fragments of diphtheria toxin), which is selective for activated T lymphocytes in psoriasis, suggesting T cells are critical for psoriasis pathogenesis [10,11] . In contrast rituximab which targets B lymphocytes is not effective in treating the disease [12] .…”

Section: Current Therapies For Psoriasis Target T Lymphocytesmentioning

confidence: 99%

Natural Killer Cells in Psoriasis

Tobin¹,

Lynch

Kirby³

et al. 2011

J Innate Immun

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Psoriasis is one of the most common immune-mediated disorders. There is evidence that it is mediated by Th1 and, more recently, Th17 cells. The cytokine pattern, particularly the dominance of TNF-α, implicates the innate immune system in psoriasis pathogenesis. Of the many components of the innate immune system known to be involved in psoriatic lesions, natural killer and natural killer T cells appear to have a unique role. We review the evidence supporting a role for natural killer cells in psoriasis.

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“…This entails the administration of fusion proteins consisting of an interleukin and a toxic polypeptide domain, as used in the transfer of pseudomonas exotoxin to IL-4R-expressing breast carcinoma cells (LeMaistre et al, 1998) and of diphtheria toxin to IL-2R-expressing lymphomas (Leland et al, 2000). Significant toxic side effects may limit this type of therapy to acutely life-threatening and incurable diseases (Bagel et al, 1998). This would almost certainly exclude atherosclerosis as a candidate ailment, although it could be applicable in a short-term strategy for the prevention of restenosis following angioplasty of atherosclerotic lesions.…”

Section: Interleukin Receptor Antagonistsmentioning

confidence: 99%