Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer

K. Naruishi, T. L. Timme, N. Kusaka, T. Fujita, G. Yang, A. Goltsov, T. Satoh, X. Ji, W. Tian, E. Abdelfattah, T. Men, M. Watanabe, K. Tabata, T. C. Thompson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We previously identified a novel p53 target gene, RTVP-1, that possesses unique cytotoxic and immunostimulatory activities which make it potentially useful for cancer gene therapy. To test the therapeutic potential of RTVP-1 in a gene-modified tumor cell-based vaccine model, we used an adenoviral vector capable of efficient transduction and expression of RTVP-1 (AdRTVP-1), together with a highly metastatic mouse prostate cancer cell line (178-2 BMA). A vaccine was prepared with 178-2 BMA cells transduced with AdRTVP-1 or a control adenoviral vector expressing β-galactosidase (Adβgal). After irradiation of the cells, syngeneic 129/Sv mice were vaccinated three times at weekly intervals. After 3 weeks, they were challenged with orthotopic 178-2 BMA cells. After 21 days, fewer than 60% of the RTVP-1-cell-vaccinated mice developed tumors compared to 100% of the control mice. The RTVP-1-cell vaccine significantly reduced primary tumor wet weight compared with control Adβgal-cell vaccine (P<0.0001 at 7 and 14 days). Experimental metastasis to lung was also significantly reduced (P=0.0377), and survival significantly increased (P=0.0002). In addition, significantly increased NK and CTL activities were demonstrated in the AdRTVP-1-cell-vaccinated mice. These findings indicate that RTVP-1 gene-modified cell-based vaccines may be useful in the prevention of recurrent prostate cancer.

Original languageEnglish
Pages (from-to)658-663
Number of pages6
JournalCancer Gene Therapy
Volume13
Issue number7
DOIs
Publication statusPublished - Jul 17 2006
Externally publishedYes

Keywords

  • Immunotherapy
  • Orthotopic
  • Prostate cancer
  • RTVP-1
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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  • Cite this

    Naruishi, K., Timme, T. L., Kusaka, N., Fujita, T., Yang, G., Goltsov, A., Satoh, T., Ji, X., Tian, W., Abdelfattah, E., Men, T., Watanabe, M., Tabata, K., & Thompson, T. C. (2006). Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer. Cancer Gene Therapy, 13(7), 658-663. https://doi.org/10.1038/sj.cgt.7700919