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Suppression of breast tumor growth by DNA vaccination against phosphatase of regenerating liver 3

Gene Therapy volume 20, pages 834–845 (2013)Cite this article

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Abstract

Phosphatase of regenerating liver (PRL)-3 is highly expressed in multiple cancers and has important roles in cancer development. Some small-molecule inhibitors and antibodies targeting PRL-3 have been recently reported to inhibit tumor growth effectively. To determine whether PRL-3-targeted DNA vaccination can induce immune response to prevent or inhibit the tumor growth, we established mouse D2F2 breast cancer cells expressing PRL-3 (D2F2/PRL-3) and control cells (D2F2/NC) with lentivirus, and constructed pVAX1-Igκ-PRL-3 plasmid (named as K-P3) as DNA vaccine to immunize BALB/c mice. We found that the K-P3 vaccine delivered by gene gun significantly prevented the growth of D2F2/PRL-3 compared with pVAX1-vector (P<0.01), but not of D2F2/NC, and improved the survival of D2F2/PRL-3-innoculated mice. Both PRL-3-targeted cytotoxic T lymphocytes (CTLs) and T-helper type 1 cell immune response (production of high levels of interferon-γ and tumor necrosis factor-α) were found to be involved in the preventive effect. Furthermore, PRL-3-targeted DNA immunization inhibited tumor growth of D2F2/PRL-3 cells in mice. We also evaluated the potential of immunization with PRL-3 protein, but no significant therapeutic or preventive effect was obtained on tumor growth. To enhance the immunity of PRL-3, we incorporated different molecular adjuvants, such as Mycobacterium tuberculosis heat-shock protein, CTL antigen 4 and M. tuberculosis T-cell stimulatory epitope (MT), into K-P3 vaccine for expressing the fusion proteins. We found that these adjuvant molecules did not significantly improve the antitumor activity of PRL-3 vaccine, but enhanced the production of PRL-3 antibodies in immunized mice. Summarily, our findings demonstrate that PRL-3-targeted DNA vaccine can generate significantly preventive and therapeutic effects on the growth of breast cancer expressing PRL-3 through the induction of cellular immune responses to PRL-3.

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Acknowledgements

We deeply appreciate Drs Z Zhi-Qian and Q-Z Zhao for providing QM7 cells and TBhsp DNA, respectively. We are most grateful for the technical help from Y Zeng, S Lian, W Xie, X Wang, Y Han, Cheng Zhang and J Wu. This study was funded by the National 973 Program of China (2009CB521805) and National Nature Science Foundation of China (81071732, 30973407).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China

    J Lv, C Liu, H Huang, L Meng, B Jiang, Y Cao, Z Zhou, T She, L Qu & C Shou

  2. Department of Minimally Invasive Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, China

    B Jiang

  3. Department of Biochemistry, Changzhi Medical College, Changzhi, Shanxi, China

    Y Cao

  4. Clinical Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China

    S Wei Song

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Lv, J., Liu, C., Huang, H. et al. Suppression of breast tumor growth by DNA vaccination against phosphatase of regenerating liver 3. Gene Ther 20, 834–845 (2013). https://doi.org/10.1038/gt.2013.5

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