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用于治疗多发性硬化症的自体T细胞疫苗接种:进展展望。

Autologous T-cell vaccination for multiple sclerosis: a perspective on progress.

作者信息

Vandenbark Arthur A, Abulafia-Lapid Rivka

机构信息

Neuroimmunology Research, Veterans Affairs Medical Center, Department of Neurology, Oregon Health & Science University, Portland, Oregon 97207, USA.

出版信息

BioDrugs. 2008;22(4):265-73. doi: 10.2165/00063030-200822040-00006.

Abstract

T-cell vaccination (TCV) is a unique approach to induce immune regulation that may have importance in the treatment of autoimmune diseases, including multiple sclerosis (MS). TCV employs a classic vaccine strategy of injecting an attenuated form of the disease-causing agent--in this case, myelin-reactive T cells--that have been selected and expanded from each MS donor and then re-injected after irradiation to induce protective immunity. This anti-T-cell immunity consistently results in selective deletion or regulation of the targeted pathogenic T cells in vivo. Longitudinal studies have established that TCV is safe and often results in a reduced relapse rate and clinical stability or improvement, at least temporarily, in the majority of treated MS patients. These results lend direct support to the involvement of inflammatory myelin-reactive T cells in the MS disease process. However, these hopeful trends reported in a number of pilot trials await validation in larger proof-of-principle trials that are now in progress.

摘要

T细胞疫苗接种(TCV)是一种诱导免疫调节的独特方法,可能对包括多发性硬化症(MS)在内的自身免疫性疾病的治疗具有重要意义。TCV采用经典的疫苗策略,即注射减毒形式的致病因子——在这种情况下是髓鞘反应性T细胞,这些细胞是从每个MS供体中挑选并扩增出来的,然后在照射后重新注射以诱导保护性免疫。这种抗T细胞免疫在体内始终会导致靶向致病性T细胞的选择性清除或调节。纵向研究已证实,TCV是安全的,并且在大多数接受治疗的MS患者中,通常会导致复发率降低以及临床稳定性或改善,至少是暂时的。这些结果直接支持了炎性髓鞘反应性T细胞参与MS疾病进程的观点。然而,一些试点试验中报告的这些令人鼓舞的趋势,有待目前正在进行的更大规模的原理验证试验加以验证。

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