Ioannides Zara A, Csurhes Peter A, Douglas Nanette L, Mackenroth Gem, Swayne Andrew, Thompson Kate M, Hopkins Tracey J, Green Kerryn A, Blum Stefan, Hooper Kaye D, Wyssusek Kerstin H, Coulthard Alan, Pender Michael P
Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
Front Neurol. 2021 Mar 15;12:652811. doi: 10.3389/fneur.2021.652811. eCollection 2021.
Increasing evidence indicates a role for Epstein-Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8 T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment. To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy. We assessed participants 2 and 3 years after completion of T cell therapy. We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8 T cell reactivity in the administered T cell product. Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.
越来越多的证据表明，爱泼斯坦-巴尔病毒（EBV）在多发性硬化症（MS）的发病机制中起作用。由于细胞毒性CD8 T细胞免疫缺陷，感染EBV的自身反应性B细胞可能在中枢神经系统中积聚。我们之前报告了自体EBV特异性T细胞疗法治疗MS 6个月后的I期临床试验结果。为了研究接受自体EBV特异性T细胞疗法的MS患者的长期预后。我们在T细胞疗法完成后2年和3年对参与者进行了评估。我们收集了第2年所有10名接受治疗的参与者以及第3年9名参与者的数据。未观察到严重的治疗相关不良事件。4名参与者在第2年至少有一些持续的临床改善，包括3名参与者疲劳减轻，2名参与者扩展残疾状态量表评分降低。3名参与者在第3年至少有一些症状持续改善。更多的持续改善与所给予的T细胞产品中更高的EBV特异性CD8 T细胞反应性相关。自体EBV特异性T细胞疗法耐受性良好，治疗后长达3年可维持一定程度的临床改善。
