Oligodeoxynucleotide CpG 7909 Delivered as Intravenous Infusion Demonstrates Immunologic Modulation in Patients With Previously Treated Non-Hodgkin Lymphoma
| Autor: | Aaron D. Bossler, Wendy L. Rasmussen, George J. Weiner, Brian K. Link, Mary Shannon, Daniel Weisdorf, Zuhair K. Ballas, Arthur M. Krieg, James E. Wooldridge |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Cytotoxicity Immunologic Male Cancer Research medicine.medical_specialty Anemia CpG Oligodeoxynucleotide Nausea Immunology Immunoglobulins Antineoplastic Agents Neutropenia Gastroenterology Recurrence Internal medicine medicine Humans Immunology and Allergy Infusions Intravenous Aged Pharmacology business.industry Lymphoma Non-Hodgkin Middle Aged medicine.disease Lymphoma Killer Cells Natural Phenotype Oligodeoxyribonucleotides CpG site Toxicity Cytokines CpG Islands Female Immunotherapy medicine.symptom business Progressive disease Follow-Up Studies |
| Zdroj: | Journal of Immunotherapy. 29:558-568 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/01.cji.0000211304.60126.8f |
| Popis: | Oligodeoxynucleotides containing CpG motifs (CpG ODN) can alter various immune cell subsets important in antibody therapy of malignancy. We undertook a phase I trial of CPG 7909 (also known as PF-3512676) in patients with previously treated lymphoma with the primary objective of evaluating safety across a range of doses, and secondary objectives of evaluating immunomodulatory effects and clinical effects. Twenty-three patients with previously treated non-Hodgkin lymphoma received up to 3 weekly 2-hour intravenous (IV) infusions of CPG ODN 7909 at dose levels 0.01 to 0.64 mg/kg. Evaluation of immunologic parameters and clinical endpoints occurred for 6 weeks. Infusion-related toxicity included grade 1 nausea, hypotension, and IV catheter discomfort. Serious adverse hematologic events observed more than once included anemia (2=Gr3, 2=Gr4), thrombocytopenia (4=Gr3), and neutropenia (2=Gr3), and were largely judged owing to progressive disease. Immunologic observations included: (1) The mean ratio of NK-cell concentrations compared with pretreatment at day 2 was 1.44 (95% CI=0.94-1.94) and at day 42 was 1.53 (95% CI=1.14-1.91); (2) NK activity generally increased in subjects; and (3) Antibody-dependent cellular cytotoxicity activity increased in select cohorts. No clinical responses were documented radiographically at day 42. Two subjects demonstrated late response. We conclude CpG 7909 can be safely given as a 2-hour IV infusion to patients with previously treated non-Hodgkin lymphoma at doses that have immunomodulatory effects. |
| Databáze: | OpenAIRE |
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