Culina Slobodan, Boitard Christian, Mallone Roberto
INSERM, U986, DeAR Lab Avenir, Saint Vincent de Paul Hospital, 82 avenue Denfert Rochereau, 75674 Paris Cedex 14, France.
Clin Dev Immunol. 2011;2011:286248. doi: 10.1155/2011/286248. Epub 2011 May 14.
The ideal drug of modern medicine is the one that achieves its therapeutic target with minimal adverse effects. Immune therapy of Type 1 diabetes (T1D) is no exception, and knowledge of the antigens targeted by pathogenic T cells offers a unique opportunity towards this goal. Different antigen formulations are being considered, such as proteins or peptides, either in their native form or modified ad hoc, DNA plasmids, and cell-based agents. Translation from mouse to human should take into account important differences, particularly in the time scale of autoimmune progression, and intervention. Critical parameters such as administration route, dosing and interval remain largely empirical and need to be further dissected. T1D staging through immune surrogate markers before and after treatment will be key in understanding therapeutic actions and to finally turn ordinary blanks into magic bullets.
现代医学的理想药物是那种能以最小的副作用实现其治疗靶点的药物。1型糖尿病(T1D)的免疫疗法也不例外,了解致病性T细胞靶向的抗原为实现这一目标提供了独特的机会。目前正在考虑不同的抗原制剂,如蛋白质或肽,无论是天然形式还是经过特别修饰的,DNA质粒以及基于细胞的制剂。从小鼠到人类的转化应考虑到重要的差异,特别是在自身免疫进展和干预的时间尺度方面。诸如给药途径、剂量和间隔等关键参数在很大程度上仍基于经验,需要进一步剖析。通过治疗前后的免疫替代标志物对T1D进行分期将是理解治疗作用并最终将普通药物转变为神奇药物的关键。