Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2 receptor targeted fusion toxin, DAB389IL-2

Phillips, S M; Bhopale, M. K.; Hilliard, Brendan; Zekavat, S A; Ali, Mohamad Anwar Ramadan; Rostami, Abdolmohamad

doi:10.1016/j.cellimm.2009.12.001

Cited by 7 publications

(8 citation statements)

References 76 publications

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“…Acute EAE (A-EAE) was induced in a group of twenty 10-week-old SJL female mice by immunizing them with 400 μg myelin basic protein purified from guinea pig spinal cord (gpMBP) 17 .…”

Section: Methodsmentioning

confidence: 99%

“…Chronic EAE (C-EAE) was induced in a group of forty 12-week-old female (SJL × PLJ) F1 mice with 5 mg mouse spinal cord homogenate (mSCH) as described previously 17 .…”

Section: Methodsmentioning

confidence: 99%

“…A daily clinical score was obtained based on a previously reported scale 17 that included the following parameters: 0 = normal; 1 = tail paralysis or tail paralysis; 2 = hind leg weakness; 3 = hind limb paralysis; 4 = fore and hind limb paralysis; 5 = death. Two trained and blinded researchers made the evaluations.…”

Section: Methodsmentioning

confidence: 99%

“…The mode of DAB 389 IL-2 action is to kill IL-2R-expressing CD4 + cells. Our previous studies demonstrated the clinical efficacy of DAB 389 IL-2 in acute EAE (A-EAE), relapsing EAE (R-EAE) and chronic EAE (C-EAE), mouse models that correspond to different courses of MS in humans 17 . Our previous report has shown that DAB 389 IL-2 indirectly suppresses the activation of macrophage CD169 + (ED3 + ) and microglia CD11b/c (OX42 + ) populations in the CNS of mice that with EAE 18 .…”

Section: Introductionmentioning

confidence: 99%

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DAB₃₈₉IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice

Bhopale

Hilliard

Constantinescu

et al. 2017

Immunopharmacology and Immunotoxicology

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Context We have reported previously that DAB389IL-2 recombinant fusion toxin targets IL-2R bearing CD4+ cells, and suppresses demyelinating disease in acute (A) - and chronic (C) - experimental autoimmune encephalomyelitis (EAE) animal models of multiple sclerosis. Objectives The present study was undertaken to investigate the effect of DAB389IL-2 treatment on various cytokine-secreting cell populations in A-EAE and C-EAE mice. Materials and methods The effects of DAB389IL-2 at doses of 200-, 800-, or 1600 kU administered i.v. on days 11–13 and 15 on the clinical score and cytokine-secreting cell populations were examined using flow cytometry. Results C-EAE mice treated with 1600 kU DAB389IL-2, but not A-EAE mice treated with 800 kU had significantly reduced disease. The CD3+CD25+ sub-population in spleens and spinal cords of A-EAE mice treated with 800 kU DAB389IL-2 was increased, whereas in C-EAE mice treated with 1600 kU this population was decreased. DAB389IL-2 treatment reduced CD3+CD4+, CD3+CD8+, CD4+CD8+, CD3+IL-2+, CD3+IFN-γ+ and CD3+TNF-α+ T cell subpopulations in the spinal cord in A-EAE, and C-EAE mice on day 16. CD11b+ macrophages that were IL-2-, IFN-γ-, and TNF-α-positive were reduced in A-EAE mice. DAB389IL-2 treatment reduced CD19+ B-cells positive for IL-2 or CD11b+ in the spinal cord in acute and chronic disease. DAB389IL-2 treatment also reduced lymph node CD3+CD8+, CD4+CD8+, CD3+CD25+ populations on day 16, and lymph node CD3+IL-10+ and peripheral blood CD3+CD25+ populations on day 24. Discussion and conclusions Our study demonstrates that DAB389IL-2 fusion toxin suppresses EAE in a dose-dependent manner, and alters inflammatory cell sub-populations during disease development.

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“…Acute EAE (A-EAE) was induced in a group of twenty 10-week-old SJL female mice by immunizing them with 400 μg myelin basic protein purified from guinea pig spinal cord (gpMBP) 17 .…”

Section: Methodsmentioning

confidence: 99%

“…Chronic EAE (C-EAE) was induced in a group of forty 12-week-old female (SJL × PLJ) F1 mice with 5 mg mouse spinal cord homogenate (mSCH) as described previously 17 .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

DAB₃₈₉IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice

Bhopale

Hilliard

Constantinescu

et al. 2017

Immunopharmacology and Immunotoxicology

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“…Additional oncologic use includes recurrent and refractory chronic lymphocytic leukemia, non-Hodgkin's B cell lymphoma, and human T cell lymphotropic virus-1-associated adult T cell leukemia/lymphoma (21). Potential additional uses of denileukin diftitox include the therapy of graft-versus-host disease and autoimmune disorders such as psoriasis, rheumatoid arthritis, and systemic lupus (22,23).…”

mentioning

confidence: 99%

The IL-2 Diphtheria Toxin Fusion Protein Denileukin Diftitox Modulates the Onset of Diabetes in Female Nonobese Diabetic Animals in a Time-Dependent Manner and Breaks Tolerance in Male Nonobese Diabetic Animals

Zinser

Rößner²,

Littmann³

et al. 2012

The Journal of Immunology

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Denileukin diftitox, also known as DAB389IL-2 or Ontak, is a fusion protein toxin consisting of the full-length sequence of the IL-2 protein and as toxophore the truncated diphtheria toxin. As a consequence, it delivers the toxic agent to CD25-bearing cells, whereby CD25 represents the high-affinity α-subunit of the IL-2 receptor. Initially it was developed for the treatment of patients with cutaneous T cell lymphoma. Meanwhile, denileukin diftitox is also used as an adjuvant in other tumor therapies and neoplastic disorders. In this study, to our knowledge we report for the first time that denileukin diftitox has also dramatic effects regarding the pathology of type 1 diabetes using the NOD mouse model. Repeated injections of denileukin diftitox into female NOD mice at 12 wk of age led to a clear acceleration of disease onset, whereas injection at 7 wk of age did not. Using male NOD mice, which are much less susceptible to diabetes, we demonstrate that the injection of denileukin diftitox leads to a dramatic development of type 1 diabetes within days after injection, thereby obviously breaking pre-existing tolerance mechanisms. This is accompanied by an increased IFN-γ production of autoreactive splenic cells and a decreased presence of regulatory CD4+CD25+Foxp3+ T cells. In contrast, transfer of CD4+CD25+Foxp3+ T cells could correct the defect after denileukin diftitox treatment. Furthermore, whereas IFN-γ production was increased in the pancreata of treated animals, insulin expression was strongly reduced. These finding should be considered when denileukin diftitox is used for the treatment of patients suffering from tumors and/or autoimmune disorders.

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Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis

Saksida¹,

Miljković²,

Timotijević³

et al. 2013

Journal of Neuroimmunology

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Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2 receptor targeted fusion toxin, DAB389IL-2

Cited by 7 publications

References 76 publications

DAB₃₈₉IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice

DAB₃₈₉IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice

The IL-2 Diphtheria Toxin Fusion Protein Denileukin Diftitox Modulates the Onset of Diabetes in Female Nonobese Diabetic Animals in a Time-Dependent Manner and Breaks Tolerance in Male Nonobese Diabetic Animals

Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis

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Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2 receptor targeted fusion toxin, DAB389IL-2

Cited by 7 publications

References 76 publications

DAB389IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice

DAB389IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice

The IL-2 Diphtheria Toxin Fusion Protein Denileukin Diftitox Modulates the Onset of Diabetes in Female Nonobese Diabetic Animals in a Time-Dependent Manner and Breaks Tolerance in Male Nonobese Diabetic Animals

Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis

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Product

Resources

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DAB₃₈₉IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice

DAB₃₈₉IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice