Lutterotti Andreas, Martin Roland
Clinical Department of Neurology, Innsbruck Medical University, Innsbruck , Austria.
Expert Opin Investig Drugs. 2014 Jan;23(1):9-20. doi: 10.1517/13543784.2014.844788. Epub 2013 Oct 23.
Inhibition of self-reactive T cells through induction of antigen-specific immune tolerance holds the promise of effective treatment of autoimmune pathology with few side effects and preservation of normal immune functions. In multiple sclerosis (MS) several approaches have been tested already in clinical trials or are currently ongoing with the aim to inhibit myelin-reactive immune responses.
This article provides an overview of the recent and ongoing strategies to inhibit specific immune responses in MS, including different applications of myelin peptide-based approaches, T-cell vaccination, DNA vaccination and antigen-coupled cells.
Despite difficulties in translation of antigen-specific therapies in MS, novel approaches have the potential to effectively induce immune tolerance and ameliorate the disease. To improve efficacy of treatments, future trials should include patients in the early phases of the disease, when the autoimmune response is predominant and immune reactivity still focused. The target antigens are not fully defined yet, and robust immunomonitoring assays should developed to provide mechanistic proof of concept in parallel to showing efficacy with respect to inhibiting inflammatory disease activity in the central nervous system (CNS).
通过诱导抗原特异性免疫耐受来抑制自身反应性T细胞,有望有效治疗自身免疫性疾病,且副作用少并能保留正常免疫功能。在多发性硬化症(MS)中,已有几种方法在临床试验中进行了测试,或目前正在进行测试,目的是抑制髓鞘反应性免疫反应。
本文概述了近期和正在进行的抑制MS中特异性免疫反应的策略,包括基于髓鞘肽方法的不同应用、T细胞疫苗接种、DNA疫苗接种和抗原偶联细胞。
尽管在MS中进行抗原特异性治疗存在困难,但新方法有潜力有效诱导免疫耐受并改善疾病。为提高治疗效果,未来试验应纳入疾病早期阶段的患者,此时自身免疫反应占主导且免疫反应仍集中。目标抗原尚未完全明确,应开发强大的免疫监测检测方法,以便在证明抑制中枢神经系统(CNS)炎症疾病活动有效性的同时,提供概念验证的机制证据。