Vudattu Nalini K, Herold Kevan C
Yale University, Department of Immunobiology and Internal Medicine , 300 George St, #353E, New Haven, CT 06520 , USA +1 203 785 6507 ;
Expert Opin Biol Ther. 2014 Mar;14(3):377-85. doi: 10.1517/14712598.2014.881797.
Type 1 diabetes is an organ-specific autoimmune disease, characterized by selective destruction of insulin-producing pancreatic β-cells by T-cell-mediated inflammation. Beginning with studies of cyclosporin A in the 1980s, but with more activity in the past decade, there have been a number of clinical trials to test whether immunotherapies can arrest the decline in C-peptide, which is associated with progression of type 1 diabetes leading to the metabolic instability that characterizes the disease. One of the most promising agents, teplizumab , is an FcR-nonbinding anti-CD3 monoclonal antibody that has been tested in Phase II - III clinical trials and was shown to preserve the C-peptide levels and reduce the need for exogenous insulin.
In this review, we discuss the recent update on clinical data obtained from trials of teplizumab in type 1 diabetes, the drug's postulated mechanism of action and the identification of responders to therapy. We highlight the results of recent trials as well as the lessons that have been learned from the clinical trials involving selection of end points and the inclusion of diverse study populations.
Teplizumab has been shown to preserve β cell function in patients; however, it does not represent a 'cure' for patients, and its efficacy does entail a significant advance in arresting the progression of the disease toward complete insulin deficiency and reliance on exogenous insulin.
1型糖尿病是一种器官特异性自身免疫性疾病，其特征是T细胞介导的炎症选择性破坏产生胰岛素的胰腺β细胞。从20世纪80年代对环孢素A的研究开始，在过去十年中这类研究更为活跃，已经有多项临床试验来测试免疫疗法是否能够阻止C肽水平下降，C肽水平下降与1型糖尿病进展相关，会导致该疾病特有的代谢不稳定。最有前景的药物之一替普珠单抗是一种不结合FcR的抗CD3单克隆抗体，已在II - III期临床试验中进行了测试，结果显示它能维持C肽水平并减少对外源胰岛素的需求。
在本综述中，我们讨论了替普珠单抗治疗1型糖尿病的试验所获得临床数据的最新情况、该药物假定的作用机制以及治疗反应者的识别。我们强调了近期试验的结果以及从涉及终点选择和纳入不同研究人群的临床试验中学到的经验教训。
替普珠单抗已被证明可保留患者的β细胞功能；然而，它并非对患者的“治愈”方法，其疗效确实在阻止疾病进展至完全胰岛素缺乏和依赖外源胰岛素方面取得了重大进展。
