CAR-T在中枢神经系统自身免疫细胞B细胞耗竭
文摘
客观的评估嵌合抗原受体(车)- t细胞介导的B细胞耗竭在实验性自身免疫性脑脊髓炎(运算单元)。
背景CAR-T细胞是自体T细胞表达non-MHC目标抗原特异性受体。我们测试是否anti-CD19 CAR-T细胞,彻底耗尽人类B细胞数量比单克隆抗体(mab),又一次重复的有利影响B细胞耗竭。在实验性自身免疫性脑脊髓炎
设计/方法Anti-CD19 CAR-T细胞或控制T细胞过表达绿色荧光蛋白被转移到女性野生型C57BL / 6小鼠使用环磷酰胺。运算单元是由免疫诱导与重组人类(rh)髓少突细胞蛋白质(MOG) (B cell-dependent)或MOG肽(p) - 55 (B cell-independent)。老鼠评估每日和每周临床体征的实验性自身免疫性脑脊髓炎外围B和T细胞计数。B细胞水平,T细胞免疫调制和组织学评估疾病和峰值终止。
结果在,rhMOG-induced实验性自身免疫性脑脊髓炎临床分数和组织学淋巴细胞浸润减少小鼠接受环磷酰胺和要么anti-CD19 CAR-T细胞或T细胞的控制。B细胞耗竭观察外周淋巴组织和小鼠的中枢神经系统(CNS)处理anti-CD19汽车T细胞,类似的影响anti-CD20马伯。没有区别在T细胞调制包括Th1或Th17人口,但有一个趋势Treg人口增加周边和中枢神经系统anti-CD19 CAR-T控制细胞和T细胞治疗的动物。临床评分和组织学p35-55-induced疾病没有治疗组之间的差异。
结论Anti-CD19 CAR-T细胞彻底耗尽B细胞外围和中枢神经系统内。治疗也导致那么严重rhMOG-induced疾病,但它是独立于B细胞耗竭。我们的结果符合人类的数据表明anti-CD19 CAR-T细胞耗尽B细胞在隔间,这表明他们可能持有承诺进步的女士。
脚注
披露:古普塔博士没有披露。米洛斯·西米奇已经收到了来自加州大学旧金山分校的支持和nms的研究。米洛斯·西米奇已收到知识产权利益从发现或技术有关卫生保健。莎朗萨根没有披露。Duecker先生没有披露。女士牧羊人没有披露。雷蒙德·索贝尔non-compensated关系为与神经病理学和实验神经病学杂志》副主编,河畔是相关利益或活动。首页豪泽博士已经收到个人薪酬在500 - 4999美元的范围作为顾问NGM生物。豪泽博士已经收到个人补偿的范围0 - 499美元为科学顾问或服务数据安全监测委员会遭受沙尘暴。豪泽博士已经收到个人补偿的范围0 - 499美元为科学顾问或服务数据安全监测委员会Alector。 Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities. Wendell Lim has nothing to disclose. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from UCSF Weill Institute for Neurosciences. The institution of Dr. Wilson has received research support from Novartis. Dr. Wilson has received personal compensation in the range of $5,000-$9,999 for serving as a Expert Witness with US Dept of Justice. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genentech. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Alexion.
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