CpG 2006 has been shown to induce anti-tumor immune responses in a variety of tumor model systems. We have previously shown that CpG 2006 in combination with chemotherapy is effective in improving survival in murine rhabdomyosarcoma. To further investigate the anti-tumor effects of CpG 2006 in the setting of minimal residual disease we used CpG as a single agent and in combination with chemotherapy, cellular and dendritic cell vaccines. Cohorts of mice were injected in the hind limb muscle with the rhabdomyosarcoma cell line, 76-9. Tumor +/− the draining inguinal lymph node was resected at day 14. Mice receiving CpG had significantly (p = 0.04) improved survival if the draining lymph node was resected but not if the lymph node was left in situ. This improvement in survival in the mice receiving CpG correlated with a significantly higher production of IFN-gamma and TNF-alpha as well as a 3 fold increase in the number of tumor specific cytotoxic T-cell precursors in the spleen. To further investigate the anti-tumor effects of CpG in combination with chemotherapy and cellular therapies we utilized the same surgical resection model, leaving the draining lymph node in situ as CpG alone failed to improve survival in this group. In combination with the chemotherapy cyclophosphamide survival was significantly improved compared to mice receiving either CpG or chemotherapy alone (p = 0.02 and p = 0.05). In combination with irradiated cellular vaccine or dendritic cell vaccine administered subQ 1 and 8 days after surgery in combination with CpG, mice receiving the combination therapy had significantly improved survival compared to either CpG or vaccine alone. These data demonstrate that CpG 2006 in combination with strategies active in cancer therapy are potent adjuvants and may add to the therapeutic potential of modalities currently in clinical practice for solid tumors.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]