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Immunostimulatory Agent Evaluation: Lymphoid Tissue Extraction and Injection Route-Dependent Dendritic Cell Activation
Published on: September 16, 2018
Immunostimulatory and anti-neoplasm effects of a novel palindrome CpG oligodeoxynucleotide in mice
Hai-yan Du1, Li-hou Dong, Bi-jun Zhao
1Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Aim:
DNAs containing unmethylated CpG motifs can stimulate innate and adaptive immunity. The aim of this study was to investigate the immunostimulatory and anti-neoplasm effects of a novel CpG oligodeoxynucleotide, ODN10, in tumor-bearing mice.
Methods:
B16 melanoma-bearing C57BL/6 mice were administered ip or sc with ODN10 or conventional CpG ODN1826 on the indicated days post inoculation. The animal survival rate and the inhibitory effect on tumor growth were observed in vivo. B and T lymphocyte proliferation, natural killing cell cytotoxicity and the phagocytic ability of peritoneal macrophages from the animals were determined using [(3)H]-thymidine incorporation assay, 4-h (51)Cr release assay and neutral red chromometry method, respectively. The serum levels of IL-12, IL-4 and IgE were quantified using ELISA assays. Histological examination of tumor tissues was performed after HE staining, and the expression of PCNA, CD63, and CD80 in tumor tissues was analyzed with immunohistochemistry.
Results:
ODN10 (1, 5 and 25 mg/kg) significantly inhibited the growth and metastasis of the tumor, and significantly prolonged the survival of tumor-bearing mice, as compared with ODN1826. The immune status was suppressed in tumor-bearing mice. Both ODN10 and ODN1826 significantly reversed the suppressed immunoactivities in tumor-bearing mice, which included promoting B and T lymphocyte proliferation, enhancing NK cell and peritoneal macrophage activities, inducing IL-12 secretion and inhibiting IL-4 and IgE secretion. Further, CpG ODNs decreased PCNA and CD63 expression while induced expression of CD80. ODN10 presented more potent activity, and displayed the most prominent immunostimulatory potential.
Conclusion:
ODN10 produces prominent immunomodulatory effects on cellular immunity in tumor-bearing mice, which might help reverse the established Th2-type responses to the Th1-type responses, thus may be used as a potent anti-tumor immunotherapy agent or adjuvant.
Insights
A novel CpG oligodeoxynucleotide, ODN10, demonstrated significant anti-tumor effects by enhancing immune responses in tumor-bearing mice. This immunotherapy agent shows potent potential for cancer treatment by modulating cellular immunity.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Unmethylated CpG motifs in DNA stimulate innate and adaptive immunity.
- CpG oligodeoxynucleotides (ODNs) are recognized for their immunostimulatory properties.
Purpose of the Study:
- To evaluate the immunostimulatory and anti-neoplasm effects of a novel CpG ODN, ODN10.
- To compare ODN10 with a conventional CpG ODN (ODN1826) in a tumor-bearing mouse model.
Main Methods:
- B16 melanoma-bearing mice were treated with ODN10 or ODN1826.
- Evaluated tumor growth, survival rates, lymphocyte proliferation, NK cell cytotoxicity, and macrophage phagocytic activity.
- Assessed serum cytokine levels (IL-12, IL-4, IgE) and tumor tissue markers (PCNA, CD63, CD80).
Main Results:
- ODN10 significantly inhibited tumor growth, metastasis, and prolonged survival compared to ODN1826.
- Both ODNs reversed immunosuppression in tumor-bearing mice by enhancing immune cell activity and modulating cytokine profiles.
- ODN10 exhibited more potent immunostimulatory activity, decreasing PCNA/CD63 and increasing CD80 expression in tumors.
Conclusions:
- ODN10 demonstrates significant immunomodulatory effects on cellular immunity in tumor-bearing mice.
- It may reverse Th2-type responses to Th1-type responses, indicating potential as an anti-tumor immunotherapy agent or adjuvant.

