The effect of CpG ODNs does not require direct ALL stimulation. Mice bearing 380 (directly responsive to CpG ODNs) or 697 (unresponsive to CpG ODNs) ALL cell lines were injected with CpG ODNs or PBS 2, 10, and 20 days after inoculation with leukemia cells (indicated by arrows) and monitored for morbidity and survival. (A) Survival curves of cell line–bearing mice. PBS-treated mice are indicated with a dashed line and CpG ODN-treated mice are indicated with a solid line. (P < .002 for 380 and P = .002 for 697; n = 5 mice/group). (B) Leukemia burden in the bone marrow of mice from panel A, measured at time of death. (C) Mouse cytokines IL-12p70 and IFN-γ (n = 6), and IFN-α (n = 4) present in the serum of PBS- and CpG-treated leukemia-free NOD/SCID mice. Bars indicate mean values for each group. **P < .005, *P < .05.