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

Claudio G. Brunstein, Jeffrey S. Miller, Qing Cao, David H. McKenna, Keli L. Hippen, Julie Curtsinger, Todd DeFor, Bruce L. Levine, Carl H. June, Pablo Rubinstein, Philip B. McGlave, Bruce R. Blazar, John E. Wagner

Research output: Contribution to journalArticle

681 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1061-1070
Number of pages10
JournalBlood
Volume117
Issue number3
DOIs
StatePublished - Jan 20 2011

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