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CpG oligodeoxynucleotides augment antitumor efficacy of folate receptor α based DNA vaccine
Zheng Qiu1, Lijun Xing1, Xueqing Zhang1
1School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
Abstract:
Folate receptor α (FRα) is overexpressed in a variety of solid tumors and has become an attractive target antigen for immunotherapy purposes. A DNA vaccine was generated by ligation of FRα cDNA into the eukaryotic vector pcDNA3.1. Expression of FRα was confirmed in transiently transfected B16 cells. B16 cell lines that stably express FRα were set up by G418 selection. A total of 100 µg purified plasmid DNA alone or in combination with CpG oligodeoxynucleotides (CpG ODN) was injected intramuscularly in C57BL/6 mice four times at one week intervals. ELISA analysis confirmed that high titers of antibodies against FRα existed in the sera of the experimental animals. Specific cytotoxic T lymphocyte activity against FRα-expressing B16 cells was found and FRα specific lymphocyte proliferation was detected. Coinjection of CpG ODN increased both humoral and cellular immune responses. In the protective model, in which C57BL/6 mice were immunized with the FRα DNA vaccine four weeks before tumor cell inoculation, the growth of tumor was significantly inhibited, and the presence of CpG ODN further increased the inhibitory effect. FRα DNA vaccine alone did not show a significant inhibitory effect in the therapeutic model, in which the DNA vaccine was immediately injected after tumor inoculation. However, FRα DNA vaccine plus CpG ODN showed a significant inhibitory effect in tumor growth. Survival curves for both animal experiments confirmed that mice immunized with pcDNA3.1/FRα plus CpG ODN had a significantly prolonged survival period than that of the pcDNA3.1 control group, the CpG ODN group or the pcDNA3.1/FRα group. The above showed that human FRα based DNA vaccination with CpG ODN as an adjuvant was effective in growth inhibition of a FRα expressing tumor in mice and deserves further evaluation as a possible immunotherapy.
Insights
A DNA vaccine targeting folate receptor α (FRα) effectively inhibited tumor growth in mice. Combining the FRα DNA vaccine with CpG oligodeoxynucleotides (CpG ODN) as an adjuvant enhanced both immune responses and therapeutic outcomes.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Folate receptor α (FRα) is overexpressed in various solid tumors, making it a promising target for cancer immunotherapy.
- DNA vaccines offer a potential strategy for cancer treatment by eliciting immune responses against tumor-associated antigens.
Purpose of the Study:
- To evaluate the efficacy of a DNA vaccine encoding human FRα, with or without CpG oligodeoxynucleotides (CpG ODN) as an adjuvant, in inhibiting the growth of FRα-expressing tumors in a mouse model.
- To assess the impact of CpG ODN on both humoral and cellular immune responses generated by the FRα DNA vaccine.
Main Methods:
- A DNA vaccine construct (pcDNA3.1/FRα) was created and expressed in B16 cells.
- C57BL/6 mice were immunized intramuscularly with the DNA vaccine, alone or with CpG ODN, and immune responses were analyzed.
- Tumor growth inhibition was assessed in both protective and therapeutic models following vaccination.
- Survival rates were evaluated in vaccinated mice challenged with tumors.
Main Results:
- Humoral immune responses, including high-titer antibodies against FRα, and cellular immune responses, such as cytotoxic T lymphocyte activity and lymphocyte proliferation, were detected.
- Coinjection with CpG ODN significantly boosted both humoral and cellular immune responses.
- The FRα DNA vaccine significantly inhibited tumor growth in the protective model, with further enhancement when combined with CpG ODN.
- In the therapeutic model, the combination of FRα DNA vaccine and CpG ODN demonstrated significant tumor growth inhibition and prolonged survival.
Conclusions:
- Human FRα-based DNA vaccination, particularly when combined with CpG ODN as an adjuvant, is effective in inhibiting the growth of FRα-expressing tumors in mice.
- This combination strategy shows promise as a potential immunotherapy for FRα-overexpressing solid tumors and warrants further investigation.
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