Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients.
Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients.
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DOI：
10.2337/dc11-0472
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发表时间：
2011-09
期刊：
影响因子：
16.2
通讯作者：
Trucco M
中科院分区：
文献类型：
--
作者：
Giannoukakis N;Phillips B;Finegold D;Harnaha J;Trucco M
树突状细胞选择性抑制自身免疫的安全性，特别是在1型糖尿病中，从未被确定。我们研究了自体树突状细胞的安全性，稳定到免疫抑制状态，在成年1型糖尿病患者。进行了一项随机、双盲、I期研究。总共10名年龄在18岁至60岁之间、没有任何其他已知或怀疑的健康状况的、其他方面通常健康的、需要胰岛素的1型糖尿病患者接受了自体树突状细胞，这些自体树突状细胞未经操作或离体工程化以达到免疫抑制状态。每2周一次在腹部皮内施用一千万个细胞，总共施用四次。主要终点是根据医生的总体评估、血液学、生化和免疫监测确定12个月内发生不良事件的患者比例。树突状细胞是安全耐受的。在整个研究期间，任何患者均未发生明显的不良事件。除了外周B220+ CD 11 c − B细胞频率显著增加（主要见于树突状细胞给药期间的工程化树突状细胞接受者）外，其他免疫群体或生化、血液学和免疫生物标志物与基线相比无统计学相关差异。用天然状态或离体定向致耐受性免疫抑制状态的自体树突状细胞治疗是安全的且耐受性良好。至少在1型糖尿病自身免疫中，树突状细胞上调了潜在有益的B220+ CD11c− B细胞群体的频率。
The safety of dendritic cells to selectively suppress autoimmunity, especially in type 1 diabetes, has never been ascertained. We investigated the safety of autologous dendritic cells, stabilized into an immunosuppressive state, in established adult type 1 diabetic patients. A randomized, double-blind, phase I study was conducted. A total of 10, otherwise generally healthy, insulin-requiring type 1 diabetic patients between 18 and 60 years of age, without any other known or suspected health conditions, received autologous dendritic cells, unmanipulated or engineered ex vivo toward an immunosuppressive state. Ten million cells were administered intradermally in the abdomen once every 2 weeks for a total of four administrations. The primary end point determined the proportion of patients with adverse events on the basis of the physician’s global assessment, hematology, biochemistry, and immune monitoring for a period of 12 months. The dendritic cells were safely tolerated. There were no discernible adverse events in any patient throughout the study. Other than a significant increase in the frequency of peripheral B220+ CD11c− B cells, mainly seen in the recipients of engineered dendritic cells during the dendritic cell administration period, there were no statistically relevant differences in other immune populations or biochemical, hematological, and immune biomarkers compared with baseline. Treatment with autologous dendritic cells, in a native state or directed ex vivo toward a tolerogenic immunosuppressive state, is safe and well tolerated. Dendritic cells upregulated the frequency of a potentially beneficial B220+ CD11c− B-cell population, at least in type 1 diabetes autoimmunity.
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影响因子：
32.4
作者：
Yanaba, Koichi;Bouaziz, Jean-David;Tedder, Thomas F.
通讯作者：
Tedder, Thomas F.
影响因子：
15.3
作者：
Dhodapkar, M V;Steinman, R M;Krasovsky, J;Munz, C;Bhardwaj, N
通讯作者：
Bhardwaj, N
DOI：
10.1196/annals.1288.012
发表时间：
2003-01-01
期刊：
IMMUNOLOGY OF DIABETES II: PATHOGENESIS FROM MOUSE TO MAN
影响因子：
--
作者：
Eisenbarth, GS
通讯作者：
Eisenbarth, GS
DOI：
10.1016/s0169-2607(99)00037-1
发表时间：
2000-03-01
影响因子：
6.1
作者：
Lazaridis, E;Gonin, R
通讯作者：
Gonin, R
DOI：
10.4049/jimmunol.181.10.6923
发表时间：
2008-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Yamazaki S;Dudziak D;Heidkamp GF;Fiorese C;Bonito AJ;Inaba K;Nussenzweig MC;Steinman RM
通讯作者：
Steinman RM