Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-α/β–inducible gene expression, without significant toxicity
| العنوان: | Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-α/β–inducible gene expression, without significant toxicity |
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| المؤلفون: | Helen H. Kim, Paul Sims, Mary McCauley, Jonathan W. Friedberg, Robert L. Coffman, Arnold S. Freedman, Lee M. Nadler, Edith M. Hessel, David C. Fisher |
| المصدر: | Blood. 105:489-495 |
| بيانات النشر: | American Society of Hematology, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Adult, Male, CpG Oligodeoxynucleotide, medicine.medical_treatment, Immunology, Gene Expression, Antineoplastic Agents, Biology, Biochemistry, Antibodies, Monoclonal, Murine-Derived, Immune system, Interferon, medicine, Humans, Aged, Antibody-dependent cell-mediated cytotoxicity, Lymphoma, Non-Hodgkin, Antibodies, Monoclonal, Interferon-alpha, Interferon-beta, Cell Biology, Hematology, Immunotherapy, Middle Aged, medicine.disease, Lymphoma, Treatment Outcome, Real-time polymerase chain reaction, Oligodeoxyribonucleotides, CpG site, Female, Rituximab, Biomarkers, medicine.drug |
| الوصف: | 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-γ (IFN-γ) 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. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::681cf9fbf9c5cddf59058286fd0c0a9b https://doi.org/10.1182/blood-2004-06-2156 |
| رقم الأكسشن: | edsair.doi.dedup.....681cf9fbf9c5cddf59058286fd0c0a9b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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