Abstract
Purpose
Measles vaccine is widely used in China to prevent the measles virus (MV) infection. People immunized with measles vaccine can obtain long-term protective immunity. Measles virus surface glycoprotein hemagglutinin (H) can also induce MV-specific immune responses. However, little is known about whether the existence of the protective immune system against MV in the host can exert anti-tumor effects and whether the MV-H gene can serve as a therapeutic gene.
Methods
We first vaccinated mice with measles vaccine, then inoculated them with MV-H protein-expressing tumor cells and observed the rate of tumor formation. We also treated mice with H protein-expressing tumor cells with measles vaccine and assessed tumor size and overall survival.
Results
Active vaccination using measles vaccine not only protected mice from developing tumors, but also eradicated established tumors. Measles vaccine elicited H-specific IFN-γ, TNF-α and granzyme B-producing CD8+ T cells and increased cytotoxic T lymphocyte (CTL) activity specific for H antigen, which provided a strong therapeutic benefit against H protein-expressing tumors. In addition, measles vaccine decreased the population of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs).
Conclusions
Our study demonstrated that tumor cells expressing H protein could activate the immune memory response against MV, which exerted specific anti-tumor effects, and indicated that the MV-H gene can be used as a potential therapeutic gene for cancer gene therapy.
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Acknowledgements
The authors acknowledge the generous gift of CD46 (+/+) IFNAR (−/−) transgenic mice from Professor Lieber and Professor Roma (Washington University). This work was supported by Grants from the Nature Science Foundation of China (no. 81372527) and the Nature Science Foundation of Shanghai Municipal Commission of Health and Family Planning (no. 201540373).
Funding
This work was supported by grants from the Nature Science Foundation of China (no. 81372527) and the Nature Science Foundation of Shanghai Municipal Commission of Health and Family Planning (no. 201540373).
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Author Xianghua Wu received a grant from the National Natural Science Foundation of China (Project no. 81372527). Author Xianghua Wu received a grant from the Nature Science Foundation of Shanghai Municipal Commission of Health and Family Planning (Project no. 201540373). Author Yuan Qi declares that she has no conflict of interest. Author Kailin Xing declares that she has no conflict of interest. Author Lanlin Zhang declares that she has no conflict of interest. Author Fangyu Zhao declares that she has no conflict of interest. Author Ming Yao declares that he has no conflict of interest. Author Aiqun Hu declares that he has no conflict of interest. Author Xianghua Wu declares that he has no conflict of interest.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The article does not contain any studies with human participants performed by any of the authors.
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Qi, Y., Xing, K., Zhang, L. et al. Protective immunity elicited by measles vaccine exerts anti-tumor effects on measles virus hemagglutinin gene-modified cancer cells in a mouse model. J Cancer Res Clin Oncol 144, 1945–1957 (2018). https://doi.org/10.1007/s00432-018-2720-7
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DOI: https://doi.org/10.1007/s00432-018-2720-7