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The Triterpenoid CDDO-Me Delays Murine Acute Graft-versus-Host Disease with the Preservation of Graft-versus-Tumor Effects after Allogeneic Bone Marrow Transplantation
- Source :
-
Biology of Blood & Marrow Transplantation . Jun2010, Vol. 16 Issue 6, p739-750. 12p. - Publication Year :
- 2010
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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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 10838791
- Volume :
- 16
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Biology of Blood & Marrow Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 50394060
- Full Text :
- https://doi.org/10.1016/j.bbmt.2010.01.020