CpG oligodeoxynucleotides enhance monoclonal antibody therapy of a murine lymphoma.
Bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine dinucleotides known as cytosine phosphorothioate guanine oligodeoxynucleotides (CpG ODN) can activate various immune-cell subsets, including cells that participate in antibody-dependent cell-mediated cytotoxicity (ADCC). Studies have shown that CpG ODN enhance the efficacy of antitumor monoclonal antibody (MoAb) therapy in the 38C13 murine B-cell lymphoma. We performed a series of in vivo experiments using this tumor model to better characterize combination therapy with MoAb and CpG ODN. CpG ODN enhanced the efficacy of MoAb therapy of lymphoma in a dose-dependent manner. This effect was seen whether the CpG ODN was given before or after the MoAb therapy, but was decreased when CpG ODN was given more than 2 days after MoAb therapy. Three doses of CpG ODN and MoAb were more effective than single doses. There was no obvious toxicity with multiple dosing. These studies confirm that immunostimulatory CpG ODN enhance the efficacy of MoAb therapy, and that multiple courses of combination therapy with CpG ODN can serve as an effective therapy for lymphoma. Further exploration of this potentially potent combination of treatments, including clinical evaluation, is indicated.
Warren
T L
TL
Department of Internal Medicine, University of Iowa Cancer Center, Iowa City 52242, IA, USA.
Dahle
C E
CE
Weiner
G J
GJ
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D018899:CpG Islands; D003601:Cytotoxicity Tests, Immunologic; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides