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

Cancer Gene Therapy volume 13, pages 658–663 (2006)Cite this article

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.

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Acknowledgements

This work was supported by grants from the NCI (ROI-50588) and Specialized Program for Research Excellence (SPORE, P50-58204). Portions of this work were conducted in facilities provided by the Houston VA Medical Center.

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Authors and Affiliations

  1. Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

    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

  2. Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA

    T L Timme & T C Thompson

  3. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    T C Thompson

  4. Department of Radiology, Baylor College of Medicine, Houston, TX, USA

    T C Thompson

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  1. K Naruishi
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  2. T L Timme
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  4. T Fujita
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  5. G Yang
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  7. T Satoh
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  9. W Tian
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  13. K Tabata
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  14. T C Thompson
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Correspondence to T C Thompson.

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Naruishi, K., Timme, T., Kusaka, N. et al. Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer. Cancer Gene Ther 13, 658–663 (2006). https://doi.org/10.1038/sj.cgt.7700919

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  • DOI: https://doi.org/10.1038/sj.cgt.7700919

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