In Vivo Control of Acute Lymphoblastic Leukemia by Immunostimulatory Cpg Oligonucleotides.
From: Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, University of British Columbia and British Columbia’s Children’s Hospital, Vancouver, Canada.
Blood
- Publish Date: Mar 2007
- ISSN: 0006-4971
- Volume: 109
- Issue: 5
- Pages: 2008-13
- Medium: Print
- Language: English
- Citation (JAMA): Fujii Hisaki, Trudeau Jacqueline D, Teachey David T, et al. In Vivo Control of Acute Lymphoblastic Leukemia by Immunostimulatory Cpg Oligonucleotides.. Blood Mar 2007;109:2008-13
Abstract
Despite considerable success in treating newly diagnosed childhood acute lymphoblastic leukemia (ALL), relapsed disease remains a significant clinical challenge. Using a NOD/SCID mouse xenograft model, we report that immunostimulatory DNA oligonucleotides containing CpG motifs (CpG ODNs) stimulate significant immune activity against primary human ALL cells in vivo. The administration of CpG ODNs induced a significant reduction in systemic leukemia burden, mediated continued disease control, and significantly improved survival of mice with established human ALL. The death of leukemia cells in vivo was independent of the ability of ALL cells to respond directly to CpG ODNs and correlated with the production of IL-12p70, IFN-alpha, and IFN-gamma by the host. In addition, depletion of natural killer cells by anti-asialo-GM1 treatment significantly reduced the in vivo antileukemic activity of CpG ODN. This antileukemia effect was not limited to the xenograft model because natural killer cell-dependent killing of ALL by human peripheral blood mononuclear cells (PBMCs) was also increased by CpG ODN stimulation. These results suggest that CpG ODNs have potential as therapeutic agents for the treatment of ALL.
Mesh Headings (Keywords): Adjuvants, Immunologic, Animals, Cell Line, Tumor, Disease Progression, Humans, Killer Cells, Natural, Mice, Oligodeoxyribonucleotides, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Survival Rate
Check for Full Text / PubMed Unique Identifier (PMID): 17068155
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