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Control of human mesothelin-expressing tumors by DNA vaccines

Gene Therapy volume 14, pages 1189–1198 (2007)Cite this article

Abstract

Mesothelin has been implicated as a potential ideal target antigen for the development of antigen-specific cancer immunotherapy for the control of mesothelin-expressing cancers such as ovarian cancer, mesothelioma and pancreatic adenocarcinoma. In the current study, we utilized a DNA vaccine encoding human mesothelin (pcDNA3-Hmeso) to treat C57BL/6 mice challenged with luciferase-expressing, Hmeso-expressing ovarian cancer cell line, Defb29 Vegf-luc/Hmeso. The therapeutic effect of the tumor-challenged mice was followed by noninvasive bioluminescence imaging systems. The mechanism of the antitumor effect was characterized by depletion of subsets of lymphocytes as well as adopted transfer of serum from pcDNA3-Hmeso-vaccinated mice. We found that vaccination with pcDNA3-Hmeso DNA vaccine generates a significant antitumor effect and promotes survival in mice challenged with Defb29 Vegf-luc/Hmeso. Furthermore, we found CD4+ and CD8+ T-cell immune responses as well as the humoral immune responses are important for the observed antitumor effects in vaccinated mice. Our data indicated that vaccination with DNA vaccine targeting Hmeso could generate potent antitumor effects against mesothelin-expressing tumors through both T cell-mediated immunity as well as antibody-mediated immunity.

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Acknowledgements

We thank Dr Richard Roden for helpful discussions. We acknowledge Archana Monie and Talia Hoory for the preparation of the manuscript. This work was supported by ovarian cancer grants from the Alliance for Cancer Gene Therapy (ACGT) and the NCDGG (1U19 CA113341-01).

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    C-L Chang, T-C Wu & C-F Hung

  2. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan

    C-L Chang

  3. Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T-C Wu

  4. Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T-C Wu

  5. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T-C Wu & C-F Hung

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  1. C-L Chang
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Correspondence to C-F Hung.

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Chang, CL., Wu, TC. & Hung, CF. Control of human mesothelin-expressing tumors by DNA vaccines. Gene Ther 14, 1189–1198 (2007). https://doi.org/10.1038/sj.gt.3302974

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