Conditionally Replicative Adenovirus for Prostate Cancer Therapy

摘要

Quantitative tumor transduction represents a major limitation to the achievement of meaningful clinical results in cancer gene therapy protocols. Approaches directed towards the goal of enhancing or amplifying the effects of a genetic transduction event may further enhance the potential efficacy of cancer gene therapy strategies. One way to achieve this amplification effect would be via replication of the delivered viral vector. In this approach, a conditionally replicative competent virus would be utilized to selectively replicate within the transduced tumor cells and not in normal tissues. Adenoviral vectors possess the unique attribute with respect to the in vivo gene delivery recommending their employment as conditionally replicative vectors. It is our hypothesis that a conditionally adenovirus that would replicate selectively and specifically into tumor cells could be developed and utilized as an experimental tumor therapy modality for prostate cancer. In these initial studies, we have shown that improving the infectivity of adenoviral vectors dramatically augments the oncolytic potency of CRAD agents. The establishment of this key principal now feasibilize our original goal to improve the replicative specificity of the CRADs for carcinoma of the prostate.