Combination of CpG Oligodeoxynucleotide and Anti-4-1BB Antibody in the Treatment of Multiple Hepatocellular Carcinoma in Mice.

Ma, Shizhao; Yang, Xinying; Zhou, Huifang; Zhang, Chaoqun; Kang, Jiwen; Sun, Dianxing

Background To investigate the effect of topical application of CpG oligodeoxynucleotide (CpG-ODN) combined with anti-4-1BB antibodies on mouse HCC multiple tumor-bearing models and the degree of improvement of anti-tumor immune response in mice. Materials and Methods We inoculated each BALB/c male mouse subcutaneously with one tumor in the axillae of the four limbs and divided them into four groups. We only selected the tumor-bearing part of the left lower limb for drug treatment. We measured the tumor-bearing volume of mice in each group. Then, we tested the organ coefficients of mice, the concentrations of IL-12 and IFN-γ in peripheral blood, the ratio of spleen Tregs and CD8+T cells, the spleen CTL killing activity, and the survival time of mice. Results We found that the tumor-bearing volume decreased significantly after the combination of CpG-ODN and anti-4-1BB antibody (P<0.001). The organ coefficients of treated mice were not significantly different from normal mice (P>0.05). The concentration of IL-12 and IFN-in serum and the ratio of CD8+T cells in spleen were increased, while the ratio of spleen Tregs was decreased. CTL activity of spleen was increased. The survival time of mice was significantly prolonged (P<0.001). Conclusion The treatment programme combining CpG-ODN with an anti-4-1BB antibody can significantly reduce tumor growth at the treatment site, slow the growth rate of metastases and improve host prognosis.