Type 1 Diabetes R&D Center, Novo Nordisk Inc., Seattle, WA, USA.
Clin Immunol. 2013 Dec;149(3):345-55. doi: 10.1016/j.clim.2013.02.002. Epub 2013 Feb 15.
Type 1 diabetes (T1D) results from an aberrant immunological response against the insulin-producing beta cells in the islets of the pancreas. The ideal therapy would restore immune balance in a safe and lasting fashion, stopping the process of beta cell decay. The efficacy of immune suppressive agents such as cyclosporin underscores the notion that T1D can in principle be prevented, albeit at an unacceptable long-term safety risk. Immune modulatory drugs such as monoclonal anti-CD3 antibody, on the other hand, have recently had rather disappointing results in phase 3 trials, possibly due to inadequate dosing or choice of inappropriate endpoints. Therefore, it is argued that striking the right balance between safety and efficacy, together with careful trial design, will be paramount in preventing T1D. Here we outline the concept of antigen-specific tolerization as a strategy to safely induce long-term protection against T1D, focusing on available clinical trial data, key knowledge gaps and potential future directions.
1 型糖尿病（T1D）是由于针对胰腺胰岛中产生胰岛素的β细胞的异常免疫反应引起的。理想的治疗方法将以安全且持久的方式恢复免疫平衡，阻止β细胞衰减的过程。免疫抑制剂如环孢素的疗效强调了这样一种观点，即 T1D 原则上可以预防，尽管存在不可接受的长期安全风险。另一方面，免疫调节药物，如单克隆抗 CD3 抗体，最近在 3 期临床试验中结果相当令人失望，这可能是由于剂量不足或选择不适当的终点。因此，有人认为，在预防 T1D 方面，在安全性和疗效之间取得正确平衡，以及精心的试验设计将至关重要。在这里，我们概述了抗原特异性耐受化的概念，作为一种安全诱导对 T1D 长期保护的策略，重点介绍了现有临床试验数据、关键知识空白和潜在的未来方向。
