Bottino R, Lemarchand P, Trucco M, Giannoukakis N
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Gene Ther. 2003 May;10(10):875-89. doi: 10.1038/sj.gt.3302015.
Type 1 diabetes mellitus, an autoimmune disorder is an attractive candidate for gene and cell-based therapy. From the use of gene-engineered immune cells to induce hyporesponsiveness to autoantigens to islet and beta cell surrogate transplants expressing immunoregulatory genes to provide a local pocket of immune privilege, these strategies have demonstrated proof of concept to the point where translational studies can be initiated. Nonetheless, along with the proof of concept, a number of important issues have been raised by the choice of vector and expression system as well as the point of intervention; prophylactic or therapeutic. An assessment of the current state of the science and potential leads to the conclusion that some strategies are ready for safety trials while others require varying degrees of technical and conceptual refinement.
1型糖尿病是一种自身免疫性疾病，是基因和细胞疗法颇具吸引力的候选对象。从使用基因工程免疫细胞诱导对自身抗原的低反应性，到移植表达免疫调节基因的胰岛和β细胞替代物以提供局部免疫豁免微环境，这些策略已证明具有概念验证，达到了可以启动转化研究的程度。尽管如此，随着概念验证的出现，载体和表达系统的选择以及干预时机（预防性或治疗性）引发了一些重要问题。对当前科学现状和潜在因素的评估得出结论，一些策略已准备好进行安全性试验，而另一些则需要不同程度的技术和概念完善。
