The Triterpenoid CDDO-Me Delays Murine Acute Graft-versus-Host Disease with the Preservation of Graft-versus-Tumor Effects after Allogeneic Bone Marrow Transplantation

Minghui Li, Kai Sun, Doug Redelman, Lisbeth A. Welniak, William J Murphy

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The occurrence of acute graft-versus-host disease (aGVHD) and tumor relapse represent the two major obstacles impeding the efficacy of allogeneic bone marrow transplantation (BMT) in cancer. We have previously shown that the synthetic triterpenoid 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid (CDDO) can inhibit murine early aGVHD, but antitumor effects were not assessed. In the current study, we found that a new derivative of CDDO, CDDO-Me, had an increased ability to inhibit allogeneic T cell responses and induce cell death of alloreactive T cells in vitro. Administration of CDDO-Me to mice following allogeneic BMT resulted in significant and increased protection from lethal aGVHD compared to CDDO. This correlated with reduced TNF-α production, reduced donor T cell proliferation, and decreased adhesion molecule (α4β7 integrin) expression on the donor T cells. CDDO-Me was also superior to CDDO in inhibiting leukemia growth in vitro. When CDDO-Me was administered following an allogeneic BMT to leukemia-bearing mice, significant increases in survival were observed. These findings suggest that CDDO-Me is superior to CDDO in delaying aGVHD, while preserving or possibly even augmenting GVT effects.

Original languageEnglish (US)
Pages (from-to)739-750
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume16
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Allogenetic bone marrow transplantation
  • CDDO-Me
  • Graft-versus-host disease
  • Graft-versus-tumor
  • Triterpenoid

ASJC Scopus subject areas

  • Transplantation
  • Hematology

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