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 tu mor, A/J mice were challenged by the s.c. implantation of a syngenic neurob lastoma cell line (neuro2a) and subsequently injected with CpG-ODNs in the vicinity of the tumor. Daily injections of 10 mu g CpG-ODNs for 15 days see med to be the most potent regimen, leading to the eradication of 5-mm-diame ter tumors in one-half of the animals and a significant tumor growth inhibi tion when compared with controls (88% reduction volume; P < 0.001). CpG-ODN -cured animals were further protected against a new tumor challenge. The an titumoral effect of CpG-ODNs was dependent on CpG motifs, and natural kille r 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.