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

• DOI: 10.1038/sj.cgt.7700919
• Publication Date: 2006-02-17T08:53:36Z
• Authors: 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
• Keywords: Cancer vaccine

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 beta-galactosidase (Adbetagal). 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 Adbetagal-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.