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* Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CA 94305;
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Osaka, Japan; and
Coley Pharmaceutical Group, Wellesley, MA 02481
Established widely metastatic tumor was cured in a transplanted mouse B cell lymphoma model, by the combination of chemotherapy plus intratumoral injection of oligodeoxynucleotides containing unmethylated C-G motifs (CpG). This therapeutic effect required that the CpG be injected directly into the tumor and was dependent on CD8 T cells. Although the efficacy of CpG oligodeoxynucleotides has been thought to depend on the expression of TLR9, we unexpectedly found that tumor rejection did not require host expression of TLR9. By using a TLR9-deficient tumor and a TLR9KO host, we demonstrate that TLR9 expression either by the host or the tumor is required. These results indicate that activation of Ag presentation by cells within the tumor via TLR9 stimulation can be an effective form of immunotherapy. This study forms the basis of an ongoing clinical trial in patients with lymphoma.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants CA 34233 and CA 33399 from the U.S. Public Health Service, National Institutes of Health, and by grants from the Leukemia and Lymphoma Research Foundation, and the Yu-Bechmann Foundation. R.L. is an American Cancer Society Clinical Research Professor.
2 Address correspondence and reprint requests to Dr. Ronald Levy, Division of Oncology, Department of Medicine, Center for Clinical Sciences Research, Room 1105, Stanford University Medical Center, 269 Campus Drive, Stanford, CA 94305-5151. E-mail address: levy{at}stanford.edu
3 Abbreviations used in this paper: DC, dendritic cell; KO, knockout; ODN, oligodeoxynucleotide; CTX, cyclophosphamide.
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 W. N. Haining, J. Davies, H. Kanzler, L. Drury, T. Brenn, J. Evans, J. Angelosanto, S. Rivoli, K. Russell, S. George, et al. CpG Oligodeoxynucleotides Alter Lymphocyte and Dendritic Cell Trafficking in Humans Clin. Cancer Res., September 1, 2008; 14(17): 5626 - 5634. [Abstract] [Full Text] [PDF]
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