Low doses of anti-CD3, ciclosporin A and the vitamin D analogue, TX527, synergise to delay recurrence of autoimmune diabetes in an islet-transplanted NOD mouse model of diabetes

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• 作者：F. Baeke (1)
  T. L. Van Belle (1)
  T. Takiishi (1)
  L. Ding (1)
  H. Korf (1)
  J. Laureys (1)
  C. Gysemans (1)
  C. Mathieu (1) Chantal.Mathieu@med.kuleuven.be
• 关键词：Autoimmunity &#8211 ; Combination therapy &#8211 ; Regulatory T cells &#8211 ; Type 1 diabetes &#8211 ; T cells &#8211 ; T helper skewing
• 刊名：Diabetologia
• 出版年：2012
• 出版时间：October 2012
• 年：2012
• 卷：55
• 期：10
• 页码：2723-2732
• 全文大小：919.4 KB
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• 作者单位：1. Laboratory for Clinical and Experimental Endocrinology (CEE), Campus Gasthuisberg O&N1, Herestraat 49 bus 902, 3000 Leuven, Belgium
• ISSN：1432-0428

文摘

Aims/hypothesis Anti-CD3 monoclonal antibodies remain the most promising immune therapy for reversing recent-onset type 1 diabetes. However, current clinical trials have revealed their major drawback, namely the narrow therapeutic window in which low doses are ineffective and higher doses that preserve functional beta cell mass cause side effects. Strategies that sidestep these limitations while preserving or improving anti-CD3’s therapeutic efficiency are essential. We hypothesised that combining a potent vitamin D₃ analogue (TX527), ciclosporin A (CsA) and anti-CD3 would act to lower the dose while maintaining or even boosting therapeutic efficacy to counteract autoimmune destruction of transplanted islets.