期刊
BLOOD
卷 117, 期 3, 页码 1061-1070出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-07-293795
关键词
-
类别
资金
- National Cancer Institute [P01 CA65493]
- Children's Cancer Research Fund
- National Heart, Lung and Blood Institute [N01 HB037164]
- Leukemia and Lymphoma Translational Research [R6029-07]
- National Marrow Donor Program [13 396 AM 2]
- [R01 CA105216]
- [HHSN268201000008C]
Acute graft-versus-host disease (aGVHD) is associated with high risk of morbidity and mortality and is a common complication after double umbilical cord blood (UCB) transplantation. To reduce these risks, we established a method of CD4(+)CD25(+)FoxP3(+) T regulatory cell (Treg) enrichment from cryopreserved UCB followed by a 18(+) 1-day expansion culture including anti-CD3/anti-CD28 antibody-coated beads and recombinant human interleukin-2. In a first-in-human clinical trial, we evaluated the safety profile of UCB Treg in 23 patients. Patients received a dose of 0.1-30 x 10(5)UCB Treg/kg after double UCB transplantation. The targeted Treg dose was achieved in 74% of cultures, with all products being suppressive in vitro (median 86% suppression at a 1: 4 ratio). No infusional toxicities were observed. After infusion, UCB Treg could be detected for 14 days, with the greatest proportion of circulating CD4(+)CD127(+)FoxP3(+) cells observed on day (+)2. Compared with identically treated 108 historical controls without Treg, there was a reduced incidence of grade II-IV aGVHD (43% vs 61%, P=.05) with no deleterious effect on risks of infection, relapse, or early mortality. These results set the stage for a definitive study of UCB Treg to determine its potency in preventing allogeneic aGVHD. This study is registered at http://www.clinicaltrials.gov as NCT00602693. (Blood. 2011; 117(3): 1061-1070)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据