Blood. 2004 Sep 9 [Epub ahead of print] Related Articles, Links
Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin's lymphoma: increased interferon-{alpha}/{beta}-inducible gene expression, without significant toxicity.
Friedberg JW, Kim H, McCauley M, Hessel EM, Sims P, Fisher DC, Nadler LM, Coffman RL, Freedman AS.
James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
CpG oligodeoxynucleotides (CpG-ODN) affect innate and adaptive immune responses, including antigen presentation, costimulatory molecule expression, dendritic cell maturation, and induction of cytokines enhancing ADCC. We conducted a phase I study evaluating 4 dose levels of a CpG-ODN (1018 ISS, Dynavax Technologies) with rituximab in 20 patients with relapsed NHL. Patients received CpG weekly x 4 beginning after the second of 4 rituximab infusions. Adverse events were minimal. Quantitative PCR measurements of a panel of genes inducible by CpG-ODN and interferons were performed on blood samples collected prior to and 24 hours after CpG. A dose-related increase was measured in the expression of several IFN-inducible genes following CpG, and correlated with serum levels of 2-5-OAS, a validated interferon response marker. Genes induced selectively by 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 patient biological responses to CpG therapy in a dose-related manner. Moreover, all of the genes significantly induced by this CpG are regulated by type-1 interferons, providing insights into the dominant immune mechanisms in humans. CpG treatment had no significant toxicity, providing rationale for further testing of this exciting combination immunotherapy approach to NHL.
PMID: 15358617 [PubMed - as supplied by publisher] |
