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Blood, 15 January 2005, Vol. 105, No. 2, pp. 489-495. Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2004-06-2156. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2156v1 105/2/489    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Friedberg, J. W. Articles by Freedman, A. S. Search for Related Content PubMed PubMed Citation Articles by Friedberg, J. W. Articles by Freedman, A. S. Related Collections Immunotherapy Clinical Trials and Observations Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-/–inducible gene expression, without significant toxicity Jonathan W. Friedberg, Helen Kim, Mary McCauley, Edith M. Hessel, Paul Sims, David C. Fisher, Lee M. Nadler, Robert L. Coffman, and Arnold S. Freedman From the James P. Wilmot Cancer Center, University of Rochester, NY; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; and Dynavax Technologies, Berkeley, CA. CpG oligodeoxynucleotides (CpG-ODNs) affect innate and adaptive immune responses, including antigen presentation, costimulatory molecule expression, dendritic cell maturation, and induction of cytokines enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). We conducted a phase 1 study evaluating 4 dose levels of a CpG-ODN (1018 ISS) with rituximab in 20 patients with relapsed non-Hodgkin lymphoma (NHL). Patients received CpG once a week for 4 weeks beginning after the second of 4 rituximab infusions. Adverse events were minimal. Quantitative polymerase chain reaction (PCR) measurements of a panel of genes inducible by CpG-ODN and interferons were performed on blood samples collected before and 24 hours after CpG. A dose-related increase was measured in the expression of several interferon–inducible genes after CpG and correlated with serum levels of 2'-5' oligoadenylate synthetase (OAS), a validated interferon response marker. Genes induced selectively by interferon- (IFN-) were not significantly induced by CpG. In conclusion, we have defined a set of gene expression markers that provide a sensitive measure of biologic responses of patients to CpG therapy in a dose-related manner. Moreover, all the genes significantly induced by this CpG are regulated by type 1 interferons, providing insight into the dominant immune mechanisms in humans. CpG treatment resulted in no significant toxicity, providing rationale for further testing of this exciting combination immunotherapy approach to NHL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Tse and A. A Horner Update on toll-like receptor-directed therapies for human disease Ann Rheum Dis, November 1, 2007; 66(suppl_3): iii77 - iii80. [Abstract] [Full Text] [PDF] J. P. Leonard, B. K. Link, C. Emmanouilides, S. A. Gregory, D. Weisdorf, J. Andrey, J. Hainsworth, J. A. Sparano, D. E. Tsai, S. Horning, et al. Phase I Trial of Toll-Like Receptor 9 Agonist PF-3512676 with and Following Rituximab in Patients with Recurrent Indolent and Aggressive Non Hodgkin's Lymphoma Clin. Cancer Res., October 15, 2007; 13(20): 6168 - 6174. [Abstract] [Full Text] [PDF] S. Maddipatla, F. J. Hernandez-Ilizaliturri, J. Knight, and M. S. Czuczman Augmented Antitumor Activity against B-Cell Lymphoma by a Combination of Monoclonal Antibodies Targeting TRAIL-R1 and CD20 Clin. Cancer Res., August 1, 2007; 13(15): 4556 - 4564. [Abstract] [Full Text] [PDF] A. Faith, E. Peek, J. McDonald, Z. Urry, D. F. Richards, C. Tan, G. Santis, and C. Hawrylowicz Plasmacytoid Dendritic Cells from Human Lung Cancer Draining Lymph Nodes Induce Tc1 Responses Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 360 - 367. [Abstract] [Full Text] [PDF] H. Fujii, J. D. Trudeau, D. T. Teachey, J. D. Fish, S. A. Grupp, K. R. Schultz, and G. S. D. Reid In vivo control of acute lymphoblastic leukemia by immunostimulatory CpG oligonucleotides Blood, March 1, 2007; 109(5): 2008 - 2013. [Abstract] [Full Text] [PDF] V. Damiano, R. Caputo, R. Bianco, F. P. D'Armiento, A. Leonardi, S. De Placido, A. R. Bianco, S. Agrawal, F. Ciardiello, and G. Tortora Novel Toll-Like Receptor 9 Agonist Induces Epidermal Growth Factor Receptor (EGFR) Inhibition and Synergistic Antitumor Activity with EGFR Inhibitors Clin. Cancer Res., January 15, 2006; 12(2): 577 - 583. [Abstract] [Full Text] [PDF] J. W. Friedberg Unique Toxicities and Resistance Mechanisms Associated with Monoclonal Antibody Therapy Hematology, January 1, 2005; 2005(1): 329 - 334. [Abstract] [Full Text] [PDF]

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