CpG ODNs stimulate killing of ALL by murine and human NK cells. (A) In vivo depletion of NK cells by asialo-GM1 antibody prior to CpG ODN stimulation significantly reduces antileukemia activity. Mice were injected with 697 cells and aGM1 antibody (or PBS) on day −2 and with aGM1 antibody (or PBS) every fourth day for 24 days. CpG ODN or PBS treatment was given on days 0, 12, and 20. P < .005 for CpG versus aGM1+CpG, and for aGM1+CpG versus PBS or aGM1. There were 5 mice per group. (B) Depletion of NK cells (NK dep) from human PBMCs prior to addition of CpG ODN abrogated the increase in ALL cell killing achieved using PBMCs from 3 healthy donors. Labeled 697 cells were incubated with unmanipulated PBMCs or NK-depleted PBMCs (NK dep) in the presence or absence of CpG ODN for 6 hours. The killing achieved at an effector-target ratio of 100:1 is shown. *P < .05. Results presented as mean ± SD.