Oligodeoxynucleotides containing CpG motifs can induce rejection of a neuroblastoma in mice.
Phosphorothioate oligodeoxynucleotides with CpG motifs (CpG-ODNs) activate various immune cell subsets and induce production of numerous cytokines. To evaluate whether CpG-ODNs can induce rejection of established malignant tumor, A/J mice were challenged by the s.c. implantation of a syngenic neuroblastoma cell line (neuro2a) and subsequently injected with CpG-ODNs in the vicinity of the tumor. Daily injections of 10 microg CpG-ODNs for 15 days seemed to be the most potent regimen, leading to the eradication of 5-mm-diameter tumors in one-half of the animals and a significant tumor growth inhibition when compared with controls (88% reduction volume; P<0.001). CpG-ODN-cured animals were further protected against a new tumor challenge. The antitumoral effect of CpG-ODNs was dependent on CpG motifs, and natural killer cells seemed to play a critical role in tumor rejection. We conclude that immunostimulatory CpG-ODNs may induce the rejection of established tumors and warrant further evaluation as a potential immunotherapeutic agent.
Carpentier
A F
AF
Fédération de neurologie Mazarin et INSERM U 495, Hôpital de la Pitié-Salpêtrière, Paris, France.
Chen
L
L
Maltonti
F
F
Delattre
J Y
JY
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D018899:CpG Islands / Q000235:genetics*; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000517:prevention & control*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D009838:Oligodeoxyribonucleotides