Bladder cancer has been shown to respond to therapies focusing on the immune system and may thus represent a good candidate for the use of retroviral models designed to encode for antitumor genes associated with the immune system, such as the ProT gene. ProtT stimulates T cell formation and suppresses the development of tumors. In an animal study, Shiau et al evaluated the efficacy of prothymosin alpha (ProT) as gene therapy for the treatment of bladder cancer. The researchers created a recombinant retrovirus carrying the ProT gene and injected it into mice along with bladder cancer cells. The mice on which the therapy was tested developed less and smaller tumors, and lived longer than mice injected with a control virus. However, mice with severely comprised immune systems did not respond to the therapy as well as mice with healthy immune systems, suggesting that the retroviral vector mechanism works through the immune system.
In addition, experiments with bladder cancer cell cultures showed that the anti-tumorigenic potential of ProT could be enhanced by removal of the ProT gene’s nuclear localization signal (NLS). The retrovirus to be considered for potential therapeutics against bladder cancer was designed to have the NLS DNA code deleted from its genome. Mice that were injected with retrovirus lacking the NLS code had longer survival rates than mice injected with the NLS coding retrovirus.
Thus, this study suggests that the use of retrovirus to inject the ProT gene into bladder cells, especially ProT DNA segments lacking the NLS code, is a potential therapeutic for the treatment of bladder cancer.
References
Shiau A-L, Lin P-R, Chang M-Y, & Wu C-L. “Retrovirus-mediated transfer of prothymosin gene inhibits tumor growth and prolongs survival in murine bladder cancer.” Gene Therapy 8.21 (2001):1609-1617. Online print.