Sensitization of prostate cancer cell lines to 5-fluorocytosine induced by adenoviral vector carrying a CD transcription unit

Objective To investigate the efficiency of the cytosine deaminase adenoviral/5-fluorocytosine system on prostate cancer cell lines.Methods We used cell culture, infectivity and sensitivity tests, to observe bystander effect by animal tests.Results Established prostate cancer cell lines are eventually infectible by adenoviral vector. The ratio of vector/cell at which infection occurs depends on the specific cell line. The peak of expression of the transferred cytosine deaminase gene occurred in cells at different time, but persisted beyond 11 days. These prostate cell lines are sensitized to 5-fluorocytosine by infection with adenoviral vector carrying the cytosine deaminase gene. Only 5% of the LNCap and 10% of the RM-1 cells were infected and produced 100% cell death. In the animal test, there was significant inhibition of tumor growth at a ratio of 400 vector particles/cell with the systematic treatment of 5-fluorocytosine.Conclusions Adenoviral vector carrying a cytosine deaminase transcription unit can sensitize prostate cancer cell lines to 5-fluorocytosine. The system can significantly inhibit the growth of prostatic tumors in mice.

Augmentation of antitumor effect of adenovirus-mediated CD suicide gene therapy by cotransfer of interleukin 2 gene in melanoma-bearing mice

Objective To investigate the antitumor effect of combined adenovirus encoding E. coli cytosine deaminase (AdCD) and adenovirus encoding murine interleukin 2 (AdIL 2) on murine melanoma. Methods C57BL/6 mice were inoculated s.c.with B16F10 melanoma cells and 3 days later received injections of AdCD and/or AdIL 2 at the site of tumor inoculation followed by administration of 5 flurocytosine (5FC) 300 mg/kg per day for 10 days. Results Mice receiving AdCD/5FC/AdIL2 therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5FC, AdIL2, AdlacZ/5FC, or PBS. Immunological analysis illustrated that combined treatment could enhance NK activity and CTL activity. Flow cytometry demonstrated that AdCD/5FC/AdIL2 therapy increased the expression of MHC I and CD80 molecules on freshly isolated tumor cells. The CD4 + and CD8 + T cell infiltration in the tumor increased significantly after the combined therapy. Conclusions Our data showed that combined transfer of CD suicide gene and IL 2 gene could inhibit the tumor growth more significantly. The increased specific and non specific antitumor immunity might be responsible for the enhanced therapeutic effect.