CpG oligodeoxynucleotide-induced immunity prevents growth of germinal center-derived B lymphoma cells

Therapeutic efficacy of CpG oligodeoxynucleotide (ODN) ISS 1018 was tested in a murine B cell lymphoma model. Previous studies showed that the B lymphoma cells of SJL mice stimulate vigorous proliferation of host CD4(+) TH cells that is unaccompanied by development of tumor-specific CTL. In the presence of ISS 1018, however, tumor cells stimulated high levels of CTL activity in vitro, and this cytotoxic activity was inhibited when anti-IL-12 mAb was added to the cultures. Tumor cells pre-incubated with ISS 1018 were also able to generate CTL without addition of exogenous ODN, and FACS analysis revealed that following incubation with ISS 1018 for 24 h, tumor cells exhibited upregulation of MHC I, MHC II, and co-stimulatory molecule CD80. Finally, tumor-injected mice treated with ISS 1018 showed significantly less growth of tumor cells in lymph nodes and spleen, and exhibited prolonged survival compared to mice treated with a control ODN. The documented effects of CpG ODNs to stimulate cytokines, such as IL-12, from antigen presenting cells, and to upregulate expression of MHC Class I and Class II, as well as co-stimulatory molecules on tumor cells, are also the likely mechanisms by which CTL are generated by ISS 1018 in the SJL B cell lymphoma model.