Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution.
Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution.
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DOI：
10.18632/oncotarget.26242
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发表时间：
2018-11-02
期刊：
影响因子：
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通讯作者：
Parmar S
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作者：
Kellner JN;Delemarre EM;Yvon E;Nierkens S;Boelens JJ;McNiece I;Olson A;Nieto Y;Ciurea S;Popat U;Ahmed S;Champlin R;Ramos J;Nishimoto M;Ma H;Ke Z;Thall P;Khoury JD;Negrin R;Andersson B;Parmar S
将脐带血（UCB）衍生的调节性T细胞（T细胞）与岩藻糖基转移酶一起孵育提高了它们归巢至靶组织的能力，以预防移植物抗宿主病（GVHD）。我们报告了5例患者（双脐血移植，n=2;外周血匹配无关供体移植，n=3）的结果，这些患者在供体移植前一天接受了脐血-TdR（剂量水平= 1×106/kg）输注。所有患者均接受了指定的UCB-Treg剂量，无任何输注反应。供体移植物中常规T细胞的比例比输注的UCB-T细胞高至少10倍（比例范围，12-356）。所有患者均在中位13天（范围，8-17天）植入。1例患者在第45天死于脑出血。血浆IL-10水平的双峰增加发生在第7天和第21天，并且值得注意的是，所有患者的血浆IL-2水平在第7天显著下降。所有可评价患者均发生≥ II级急性GVHD，在1年随访时，所有患者均存活且无疾病复发证据。在第7天未观察到慢性GVHD生物标志物（REG 3a和Elafin）的增加。末次随访时，所有可评价患者均停止免疫抑制。目前正在进行本临床试验的第2阶段，检查剂量水平= 1×107/kg的UCB-Treg。
Incubation of umbilical cord blood (UCB) derived regulatory T-cells (Tregs) with fucosyltransferase enzyme improves their ability to home to the target tissue to prevent graft vs. host disease (GVHD). We report results of 5 patients (Double UCB Transplant, n=2; Peripheral Blood Matched Unrelated Donor Transplant, n=3) who received UCB-Tregs (Dose level = 1×106/kg), infused one day prior to the donor graft. All patients received their designated UCB-Treg dose without any infusion reaction. The ratio of conventional T-cells in donor graft was at least 10 times higher than infused UCB-Tregs (ratio range, 12-356). All patients engrafted at median of 13 days (range, 8-17 days). One patient died due to brain hemorrhage on day 45. A bi-modal increase of plasma IL-10 level occurred on day 7 and day 21 and notably, plasma IL-2 level dropped significantly in all patients at Day 7. All evaluable patients developed ≥grade II acute GVHD and at 1 year follow up, all were alive and without evidence of disease relapse. No increase in the chronic GVHD biomarkers (REG3a and Elafin) was observed at day 7. At the time of last follow up, all evaluable patients were off immune-suppression. Stage 2 of this clinical trial examining UCB-Treg at dose level= 1×107/kg is currently underway.