HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, J. Articles by Levy, R. Search for Related Content PubMed PubMed Citation Articles by Li, J. Articles by Levy, R.

Lymphoma Immunotherapy with CpG Oligodeoxynucleotides Requires TLR9 Either in the Host or in the Tumor Itself¹

Jiali Li^*, Wenru Song^*, Debra K. Czerwinski^*, Bindu Varghese^*, Satoshi Uematsu, Shizuo Akira, Arthur M. Krieg and Ronald Levy^2,*

^* 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.

This article has been cited by other articles:

				R. Houot and R. Levy T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy Blood, April 9, 2009; 113(15): 3546 - 3552. [Abstract] [Full Text] [PDF]

				J. D. Brody, M. J. Goldstein, D. K. Czerwinski, and R. Levy Immunotransplantation preferentially expands T-effector cells over T-regulatory cells and cures large lymphoma tumors Blood, January 1, 2009; 113(1): 85 - 94. [Abstract] [Full Text] [PDF]

				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]