Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics

Blood. 2011 Jan 20;117(3):1061-70. doi: 10.1182/blood-2010-07-293795. Epub 2010 Oct 15.


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 × 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 as NCT00602693.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Proliferation*
  • Cells, Cultured
  • Cord Blood Stem Cell Transplantation / methods
  • Female
  • Fetal Blood / cytology
  • Graft vs Host Disease / immunology
  • Humans
  • Leukemia / classification
  • Leukemia / surgery
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / transplantation*
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Associated data