Abstract
Ovarian cancer is a gynecologic malignancy with a high mortality rate. In the present study, we developed a novel cell-based vaccine, Meso-VAX, to generate mesothelin antigen-specific immune responses and immunotherapy against ovarian cancer. Mesothelin, a secreted protein anchored at the cell membrane, has recently been identified as a potential new tumor antigen for ovarian cancer. In this study, mice vaccinated with Meso-VAX and adeno-associated virus (AAV)-IL-12 exhibited dramatic increases in the number of mesothelin-specific CD4+ helper and CD8+ cytotoxic T-cell precursors, higher titers of anti-mesothelin Abs and in vitro tumor killing activity, and all of these mice were tumor-free after 60 days of tumor challenge. In addition, a significant reduction in peritoneal tumors and longer survival were noted in the mice vaccinated with Meso-VAX combined with AAV-IL-12. CD4+ helper and CD8+ cytotoxic T lymphocytes were essential for the antitumor effect generated by Meso-VAX combined with AAV-IL-12. The post-vaccination sera of the mice vaccinated with Meso-VAX and AAV-IL-12 also showed mesothelin-specific complement-dependent cell-mediated cytotoxicity. Our results suggest that a Meso-VAX cell-based vaccine combined with AAV-IL-12 can generate antigen-specific immunological responses and antitumor effects on ovarian cancer.
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Acknowledgements
This work was supported in part by the 2nd and 7th core laboratory facilities of the Department of Medical Research of National Taiwan University Hospital. The lentiviral vector used to construct WF-3/Luc was obtained from the National RNAi Core Facility Platform of the Institute of Molecular Biology/Genomic Research Center, Academia Sinica. This study was supported by National Science Committee of Taiwan (NSC 100-2325-B-002-004, MOST 103-2314-B-281-008-MY3) and the National Core Facility Program for Biotechnology Grants of the National Science Committee of Taiwan (NSC 100-2319-B-001-002).
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Chang, MC., Chen, YL., Chiang, YC. et al. Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator. Gene Ther 23, 38–49 (2016). https://doi.org/10.1038/gt.2015.85
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DOI: https://doi.org/10.1038/gt.2015.85
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