Journal
BLOOD
Volume 105, Issue 2, Pages 489-495Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2004-06-2156
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Funding
- NCI NIH HHS [CA102216] Funding Source: Medline
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CpG oligocleoxynucleotides (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 (11018 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-gamma (IFN-gamma) 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 ration-ale for further testing of this exciting combination immunotherapy approach to NHL. (C) 2005 by The American Society of Hematology.
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