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In vivo bioluminescence visualization of antitumor effects by human MUC1 vaccination
Yong Hyun Jeon1, Yun Choi, Hyun Joo Kim
1Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Abstract:
Recently, the use of a cancer deoxyribonucleic acid (DNA) vaccine encoding tumor-associated antigens has emerged as an immunotherapeutic strategy. In this study, we monitored tumor growth inhibition by pcDNA3-hMUC1 immunization in mice using optical imaging. To determine the anti-hMUC1-associated immune response generated by pcDNA3.1 or pcDNA3-hMUC1, we determined the concentration of interferon-gamma (IFN-gamma) protein and CD8+IFN-gamma cell numbers among lymphocytes from the draining lymph nodes of mice immunized with pcDNA3.1 or pcDNA3-hMUC1. After subcutaneously injecting CT26/hMUC1-Fluc into mice immunized with pcDNA3-hMUC1, we monitored in vivo tumor growth inhibition using an optical imaging method. The concentration of IFN-gamma protein in pcDNA3-hMUC1 was higher than that of the pcDNA3.1 group (2.7 < or = 0.08 ng/mL and 1.6 +/- 0.07 ng/mL, respectively, p < .001. The number of hMUC1-associated CD8+IFN-gamma cells in pcDNA3-hMUC1-immunized animals was 30-fold higher than in the pcDNA3.1 group. Bioluminescent images showed tumor growth inhibition in pcDNA3-hMUC1 immunized animals up to 25 days after immunization. A good correlation (r2 = .9076: pcDNA3/hMUC1 group; r2 = .7428: pcDNA3.1 group) was observed between bioluminescence signals and tumor weights in two mice in each group. We conclude that optical bioluminescent imaging offers a useful means of monitoring the antitumor effects of cancer DNA immunization in living animals.
Insights
Cancer deoxyribonucleic acid (DNA) vaccines encoding tumor-associated antigens show promise. This study demonstrates that pcDNA3-hMUC1 immunization effectively inhibits tumor growth and elicits a robust anti-tumor immune response in mice, monitored via optical imaging.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Cancer deoxyribonucleic acid (DNA) vaccines targeting tumor-associated antigens are an emerging immunotherapeutic strategy.
- Monitoring therapeutic efficacy in vivo is crucial for vaccine development.
Purpose of the Study:
- To evaluate the tumor growth inhibition induced by pcDNA3-hMUC1 immunization in a mouse model.
- To assess the anti-hMUC1 immune response using interferon-gamma (IFN-gamma) levels and CD8+IFN-gamma cell counts.
- To validate optical imaging as a method for monitoring anti-tumor effects.
Main Methods:
- Mice were immunized with either pcDNA3.1 or pcDNA3-hMUC1.
- Immune response was assessed by measuring IFN-gamma protein concentration and CD8+IFN-gamma+ T cell numbers in draining lymph nodes.
- Tumor growth inhibition was monitored in vivo using optical bioluminescent imaging after challenging with CT26/hMUC1-Fluc cells.
Main Results:
- pcDNA3-hMUC1 immunization significantly increased IFN-gamma protein levels and CD8+IFN-gamma+ T cell numbers compared to the control group (p < .001).
- Optical imaging revealed significant tumor growth inhibition in pcDNA3-hMUC1-immunized mice for up to 25 days.
- A strong correlation was observed between bioluminescence signals and tumor weights, validating the imaging method.
Conclusions:
- pcDNA3-hMUC1 DNA vaccination effectively inhibits tumor growth and stimulates a potent anti-tumor immune response in mice.
- Optical bioluminescent imaging is a valuable tool for real-time monitoring of anti-cancer DNA vaccine efficacy in vivo.
