Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect

被引：323

作者：

Brunstein, Claudio G. ^{[1
,2
]}

Miller, Jeffrey S. ^{[1
,2
]}

McKenna, David H. ^{[3
,4
]}

Hippen, Keli L. ^{[1
,5
]}

Defor, Todd E. ^{[1
,6
]}

Sumstad, Darin ^{[1
,4
]}

Curtsinger, Julie ^{[1
,5
]}

Verneris, Michael R. ^{[1
,5
]}

MacMillan, Margaret L. ^{[1
,5
]}

Levine, Bruce L. ^{[7
,8
]}

Riley, James L. ^{[7
,8
]}

June, Carl H. ^{[7
,8
]}

Le, Chap ^{[6
,9
]}

Weisdorf, Daniel J. ^{[1
,2
]}

McGlave, Philip B. ^{[1
,2
]}

Blazar, Bruce R. ^{[1
,5
]}

Wagner, John E. ^{[1
,5
]}

机构：

[1] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA

[2] Univ Minnesota, Div Hematol Oncol & Transplantat, Minneapolis, MN USA

[3] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

[4] Univ Minnesota, Mol & Cellular Therapeut Facil, Minneapolis, MN USA

[5] Univ Minnesota, Div Pediat Blood & Marrow Transplantat, Minneapolis, MN USA

[6] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA

[7] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[8] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[9] Univ Minnesota, Div Biostat, Minneapolis, MN USA

来源：

BLOOD | 2016年 / 127卷 / 08期

基金：

美国国家卫生研究院;

关键词：

TRANSPLANTATION; EXPRESS; ADULTS;

D O I：

10.1182/blood-2015-06-653667

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB)-derived regulatory T cells (Tregs) that expanded in cultures stimulated with K562 cells modified to express the high-affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3-100x10(6) Treg/kg. The median proportion of CD4(+)FoxP3(+)CD127(-) in the infused product was 87% (range, 78%-95%), and we observed no dose-limiting infusional adverse events. Clinical outcomes were compared with contemporary controls (n = 22) who received the same conditioning regimen with sirolimus and mycophenolate mofetil immune suppression. The incidence of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 9% (95% confidence interval [CI], 0-25) vs 45% (95% CI, 24-67) in controls (P=.05). Chronic GVHD at 1 year was zero in Tregs and 14% in controls. Hematopoietic recovery and chimerism, cumulative density of infections, nonrelapse mortality, relapse, and disease-free survival were similar in the Treg recipients and controls. KT64/86-expanded UCB Tregs were safe and resulted in low risk of acute GVHD.

引用

页码：1044 / 1051

页数：8

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