文摘
摘要目的:验证的安全性和有效性的迹象的患者耐受性树突状细胞(tolDCs)在多发性硬化和视Neuromyelitis谱系障碍。
背景:多发性硬化(MS)和视Neuromyelitis谱系障碍(NMOSD)是中枢神经系统的自身免疫性疾病导致严重残疾。自身免疫反应的存在myelin-derived肽在女士和aquaporin-4 (AQP4)在人类NMOSD支持的发展tolDCs等抗原耐受诱导疗法。
设计/方法:我们进行了第一次在人类Ib期临床试验测试浓度增加自体tolDCs (50 - 300 106细胞静脉输液分为3剂次每2周)含有7髓鞘和12例aquaporin-4肽,与NMOSD 8女士和4。主要终点是干预和二级终端的安全性和耐受性临床结果(复发和残疾),成像(MRI和10月)和免疫标记(细胞子集,细胞增殖和细胞因子分泌特定肽)。
结果:治疗tolDCs耐受性良好,没有严重不良事件和therapy-related反应。患者在临床水平保持稳定的复发和残疾量表,以及成像层面。我们观察到显著增加生产的il - 10水平与肽以及PBMCs刺激Tr1的频率的增加细胞的第12周的随访。没有观察到的细胞增殖显著差异。这些研究结果验证了在另外8例(5和3女士动)治疗剂量越高,确认良好的治疗的耐受性和诱导免疫耐受的治疗。
结论:静脉注射管理peptide-loaded dc疫苗是安全的,可行的,有效地诱发抗原特异性T调节细胞il - 10生产的女士和NMOSD患者。
披露:Zubizarreta博士已经收到个人赔偿咨询、担任科学顾问委员会说,与Genzyme或其他活动,默克和Bayer-Schering生原体。Florez-Grau博士没有披露。维拉博士没有披露。大头鱼博士没有披露。西班牙博士没有披露。博士安道尔没有披露。Saiz博士已经收到个人赔偿咨询、担任科学顾问委员会说,与Merck-Serono或其他活动,赛诺菲,生原体,罗氏,TEVA,诺华和Bayer-Schering。Llufriu博士已经收到个人赔偿咨询、担任科学顾问委员会说,或其他活动Idec,诺华,Teva, Genzyme和默克公司。赛普维达博士没有披露。苍井空博士没有披露。 Dr. Martinez-Lapiscina has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC. Dr. Pulido Valdeolivas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche Spain, Genzyme-Sanofi, and Aura Innovative Robotics. Dr. Pulido Valdeolivas has received compensation for serving on the Board of Directors of Aura Innovative Robotics. Dr. Pulido Valdeolivas has received royalty, license fees, or contractual rights payments from Aura Innovative Robotics. Dr. Pulido Valdeolivas holds stock and/or stock options in Aura Innovative Robotics which sponsored research in which Dr. Pulido Valdeolivas was involved as an investigator. Dr. Pulido Valdeolivas holds stock and/or stock options in Aura Innovative Robotics. Dr. Pulido Valdeolivas has received research support from Aura Innovative Robotics. Dr. Casanova has nothing to disclose. Dr. Martinez Ginés has nothing to disclose. Dr. Tellez has nothing to disclose. Dr. Oreja-Guevara has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with received honoraria for speaking and/or consultancy from Sanofi-Genzyme, Merck, Biogen, Bayer, Celgene, Roche, Teva and Novartis. Dr. Español has nothing to disclose. Dr. Cid has nothing to disclose. Dr. Juan has nothing to disclose. Dr. Lozano has nothing to disclose. Dr. Blanco Morgado has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Novartis and Genzyme-Sanofi. Dr. Steinman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene, Merck, Coherus, and Atreca. Dr. Steinman has received compensation for serving on the Board of Directors of Atreca and Tolerion. Dr. Steinman has received royalty, license fees, or contractual rights payments from Tolerion. Dr. Steinman has received research support from Coherus and Celgene. Dr. Benitez has nothing to disclose. Dr. Villoslada has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche and Health Engineering. Dr. Villoslada has received compensation for serving on the Board of Directors of Bionure Inc, Spire Bioventures, Mint-Labs and Health Engineering.
