IL-2 immunotherapy for targeting regulatory T cells in autoimmunity
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作者:
Valentina Lykhopiy
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机构:KU Leuven-University of Leuven,Department of Microbiology, Immunology and Transplantation
Valentina Lykhopiy
Vanshika Malviya
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机构:KU Leuven-University of Leuven,Department of Microbiology, Immunology and Transplantation
Vanshika Malviya
Stephanie Humblet-Baron
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机构:KU Leuven-University of Leuven,Department of Microbiology, Immunology and Transplantation
Stephanie Humblet-Baron
Susan M. Schlenner
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机构:KU Leuven-University of Leuven,Department of Microbiology, Immunology and Transplantation
Susan M. Schlenner
机构:
[1] KU Leuven-University of Leuven,Department of Microbiology, Immunology and Transplantation
[2] argenx BV,undefined
[3] Industriepark Zwijnaarde 7,undefined
来源:
Genes & Immunity
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2023年
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24卷
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5期
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摘要:
FOXP3+ regulatory T cells (Treg) are indispensable for immune homoeostasis and for the prevention of autoimmune diseases. Interleukin-2 (IL-2) signalling is critical in all aspects of Treg biology. Consequences of defective IL-2 signalling are insufficient numbers or dysfunction of Treg and hence autoimmune disorders in human and mouse. The restoration and maintenance of immune homoeostasis remain central therapeutic aims in the field of autoimmunity. Historically, broadly immunosuppressive drugs with serious side-effects have been used for the treatment of autoimmune diseases or prevention of organ-transplant rejection. More recently, ex vivo expanded or in vivo stimulated Treg have been shown to induce effective tolerance in clinical trials supporting the clinical benefit of targeting natural immunosuppressive mechanisms. Given the central role of exogenous IL-2 in Treg homoeostasis, a new and promising focus in drug development are IL-2-based approaches for in vivo targeted expansion of Treg or for enhancement of their suppressive activity. In this review, we summarise the role of IL-2 in Treg biology and consequences of dysfunctional IL-2 signalling pathways. We then examine evidence of efficacy of IL-2-based biological drugs targeting Treg with specific focus on therapeutic candidates in clinical trials and discuss their limitations.
机构:
Washington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Ghasemi, Reza
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Lazear, Eric
Wang, Xiaoli
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机构:
Washington Univ, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Wang, Xiaoli
Arefanian, Saeed
论文数: 0引用数: 0
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机构:
Washington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Arefanian, Saeed
Zheleznyak, Alexander
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机构:
Washington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Zheleznyak, Alexander
Carreno, Beatriz M.
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机构:
Washington Univ, Dept Med, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Carreno, Beatriz M.
Higashikubo, Ryuji
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机构:
Washington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Higashikubo, Ryuji
Gelman, Andrew E.
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机构:
Washington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Washington Univ, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Gelman, Andrew E.
Kreisel, Daniel
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Washington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Washington Univ, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Kreisel, Daniel
Fremont, Daved H.
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机构:
Washington Univ, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USA
Dept Mol Microbiol & Biochem & Mol Biophys, 660 South Euclid Ave, St Louis, MO 63110 USA
Washington Univ, Sch Med, Alvin Siteman Canc Ctr, 4921 Parkview Pl, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Fremont, Daved H.
Krupnick, Alexander Sasha
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机构:
Washington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
Washington Univ, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USA
Washington Univ, Sch Med, Alvin Siteman Canc Ctr, 4921 Parkview Pl, St Louis, MO 63110 USAWashington Univ, Dept Surg, 660 South Euclid Ave, St Louis, MO 63110 USA
机构:
Kyushu Univ, Grad Sch Med Sci, Dept Canc Therapy & Res, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Canc Therapy & Res, Higashi Ku, Fukuoka 8128582, Japan
Onishi, Hideya
Morisaki, Takashi
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机构:
Fukuoka Canc Gen Clin, Fukuoka, JapanKyushu Univ, Grad Sch Med Sci, Dept Canc Therapy & Res, Higashi Ku, Fukuoka 8128582, Japan
Morisaki, Takashi
Katano, Mitsuo
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机构:
Kyushu Univ, Grad Sch Med Sci, Dept Canc Therapy & Res, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Canc Therapy & Res, Higashi Ku, Fukuoka 8128582, Japan