OncoTargets and Therapy (Jul 2020)
Combination of CpG Oligodeoxynucleotide and Anti-4-1BB Antibody in the Treatment of Multiple Hepatocellular Carcinoma in Mice
Abstract
Shizhao Ma,* Xinying Yang,* Huifang Zhou, Chaoqun Zhang, Jiwen Kang, Dianxing Sun The Liver Disease Center of PLA, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang 050082, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dianxing SunThe Liver Disease Center of PLA,The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang 050082, People’s Republic of ChinaTel +86 31187978434Email [email protected]: 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.Keywords: hepatocellular carcinoma, 4-1BB, CpG-ODN, immunity therapy
