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Establishment and evaluation of cell and animal models expressing BORIS subfamily 2 variant
Lu Qin1, Zhong-Jian Liu1, Long-Jun Xian1
1Department of Medical Biochemistry and Molecular Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.
Background:
The possibility of a cancer vaccine aimed at stimulating or mobilizing the body's immune system to control and kill tumor cells is emerging as a potential new strategy for tumor immunological therapy. CCCTC-binding Factor Like (CTCFL)/Brother of the Regulator of Imprinted Sites (BORIS), a cancer-testis antigen (CTA), has 23 mRNA splice variants classified into six subfamilies (sfs) and potentially encodes 17 distinct polypeptides. Based on our previous long-term research on hepatocellular carcinoma (HCC), we were particularly interested in whether BORIS sf2 could be a promising candidate for immunotherapy targeting liver cancer cells. Therefore, in this study, we aimed to construct an animal model to study the immunogenicity of human BORIS sf2 in murine hepatoma cells.
Methods:
We established a hepatoma cell line expressing human BORIS sf2/C68 by inserting the sequences into a lentiviral vector pLVX-EF1α-IRES-Puro carrying the puromycin resistance gene. We achieved the stabilized expression of BORIS sf2/C68 in the oncogenic Hepa1c1c7 cells through lentivirus-mediated approach. The Hepa1c1c7 cells expressing the BORIS sf2/C68 (5×106/mouse) were inoculated subcutaneously into 6-week-old C57BL/6 mice to induce the formation of tumors.
Results:
In the tumor formation experiment, the murine hepatoma cells expressing human BORIS sf2/C68 showed progressive growth in C57BL/6 mice. The animal model we constructed could be used to study the in vivo immunogenicity of the human BORIS sf2 in murine hepatoma cells.
Conclusions:
The animals bearing BORIS sf2/C68-positive tumors may serve as an animal model for studying the therapeutic potency and safety of HCC vaccine directed at the CT-antigen BORIS sf2.
Insights
Researchers developed a new animal model to test cancer vaccines. This model uses mice with tumors expressing a specific cancer-testis antigen, BORIS sf2, to study its potential for liver cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cancer vaccines represent a novel immunotherapy strategy to harness the immune system against tumor cells.
- CCCTC-binding Factor Like (CTCFL)/Brother of the Regulator of Imprinted Sites (BORIS) is a cancer-testis antigen with multiple splice variants.
- The BORIS sf2 splice variant is of particular interest for potential immunotherapy in hepatocellular carcinoma (HCC).
Purpose of the Study:
- To construct an animal model for evaluating the immunogenicity of human BORIS sf2 in murine hepatoma cells.
- To investigate BORIS sf2 as a potential target for liver cancer immunotherapy.
Main Methods:
- Established a hepatoma cell line stably expressing human BORIS sf2/C68 using a lentiviral vector.
- Utilized lentivirus-mediated gene transfer into oncogenic Hepa1c1c7 cells.
- Induced tumor formation by subcutaneously inoculating C57BL/6 mice with BORIS sf2/C68-expressing Hepa1c1c7 cells.
Main Results:
- Murine hepatoma cells expressing human BORIS sf2/C68 demonstrated progressive tumor growth in C57BL/6 mice.
- The developed animal model successfully supported tumor formation.
Conclusions:
- The constructed animal model is suitable for studying the in vivo immunogenicity of human BORIS sf2.
- This model can be used to assess the therapeutic efficacy and safety of HCC vaccines targeting the BORIS sf2 cancer-testis antigen.
