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Biol Blood Marrow Transplant. 2010 Jun;16(6):739-50. doi: 10.1016/j.bbmt.2010.01.020. Epub 2010 Mar 23.

The triterpenoid CDDO-Me delays murine acute graft-versus-host disease with the preservation of graft-versus-tumor effects after allogeneic bone marrow transplantation.

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1
Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, Nevada, USA.

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-alpha production, reduced donor T cell proliferation, and decreased adhesion molecule (alpha(4)beta(7) 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.

PMID:
20338256
PMCID:
PMC2866806
DOI:
10.1016/j.bbmt.2010.01.020
[Indexed for MEDLINE]
Free PMC Article

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