scholarly journals Ex vivo generation of umbilical cord blood T regulatory cells expressing the homing markers CD62L and cutaneous lymphocyte antigen

Oncotarget ◽  
2018 ◽  
Vol 9 (72) ◽  
pp. 33694-33701
Author(s):  
Joshua N. Kellner ◽  
Eric Yvon ◽  
Simrit Parmar
Cytotherapy ◽  
2017 ◽  
Vol 19 (2) ◽  
pp. 250-262 ◽  
Author(s):  
David H. McKenna ◽  
Darin Sumstad ◽  
Diane M. Kadidlo ◽  
Bjorn Batdorf ◽  
Colin J. Lord ◽  
...  

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 1061-1070 ◽  
Author(s):  
Claudio G. Brunstein ◽  
Jeffrey S. Miller ◽  
Qing Cao ◽  
David H. McKenna ◽  
Keli L. Hippen ◽  
...  

Abstract 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 × 105UCB 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.


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