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Updated: May 31, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
CpG oligodeoxynucleotide stimulates protective innate immunity against human renal cell carcinoma xenografted in nude
Pei-jun Zhou1, Bin-bin Ma, Wei He
1Department of Urology, Rui-jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. peijunzhou@yahoo.com
Abstract:
Renal cell carcinoma easily develops metastasis, which is highly resistant to a variety of therapies. Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are potent activators of innate and adaptive immunity. CpG ODN is inclined to be used as vaccine adjuvant or in combination with other therapies to exert antitumor effect mediated by the adaptive immunity. Herein, we examined the antitumor effect of CpG ODN monotherapy and the role of innate immunity on human RCC Caki-1 cells xenografted in nude mice. Our results indicated that the peritumoral subcutaneous injections of CpG ODN1826 once a week resulted in significant inhibition of the growth of Caki-1 xenografts compared with the control groups, and the survival of tumor-bearing mice were also prolonged significantly. When cytotoxicity of splenic cells from host mice was assessed, it was found that CpG ODN1826 significantly promoted the cytotoxicities of splenocytes targeting primary Caki-1 cells or YAC-1 cells, indicating that the activity of natural killer cells in tumor-bearing nude mice was enhanced by CpG ODN1826 monotherapy. The serum concentrations of interleukin-12 were increased in mice treated with CpG ODN1826. Thus, CpG ODN1826 monotherapy induces significant inhibitory effects on the growth of human RCC xenografted in athymic immunodeficient mice, and the tumor-bearing mice achieves long-term survival, which might be attributed to enhanced innate immunity.
Insights
CpG oligodeoxynucleotides (ODN) monotherapy significantly inhibited renal cell carcinoma (RCC) growth in mice. This treatment enhanced innate immunity, boosting natural killer cell activity and prolonging survival in tumor-bearing mice.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Renal cell carcinoma (RCC) is a metastatic cancer resistant to therapy.
- CpG oligodeoxynucleotides (ODN) activate innate and adaptive immunity.
- CpG ODN are explored as vaccine adjuvants or combination therapies for cancer.
Purpose of the Study:
- To investigate the antitumor effects of CpG ODN monotherapy.
- To determine the role of innate immunity in CpG ODN's anti-RCC activity.
- To evaluate CpG ODN1826 efficacy in a human RCC xenograft model.
Main Methods:
- Human RCC Caki-1 cells were xenografted into nude mice.
- Mice received weekly peritumoral subcutaneous injections of CpG ODN1826.
- Tumor growth, survival rates, splenocyte cytotoxicity, and serum cytokine levels were assessed.
Main Results:
- CpG ODN1826 significantly inhibited Caki-1 xenograft growth.
- CpG ODN1826 treatment significantly prolonged the survival of tumor-bearing mice.
- CpG ODN1826 enhanced natural killer cell activity and increased interleukin-12 levels.
Conclusions:
- CpG ODN1826 monotherapy demonstrates significant antitumor effects against human RCC in vivo.
- Enhanced innate immunity, particularly natural killer cell function, contributes to the therapeutic efficacy.
- CpG ODN1826 monotherapy offers a promising strategy for managing renal cell carcinoma.
