Prostate Specific Gene Therapy Using a 'Gutless' Adene-Vector Expressing Antisense TGF-Beta and PSA Promotor-Control

摘要

A gene therapy protocol that can achieve exquisite prostate cancer restricted expression of cytotoxic genes will minimize systemic side effects. Thus, we designed our prostate specific therapeutic scheme using the well- characterized Prostate Specific Antigen PSA enhancer/promoter (PSE). We have generated new constructs that increase the transcriptional activity greatly over the natural version. High in vivo expression coupled with its specificity will hold the best chance for effective therapy in patients. We have taken a combined approach of targeted cytotoxicity and generation of a tumor-specific immune response with reversal of local immunosuppression. We aim to achieve this gene therapy scheme with the most advanced gutless' adenovector (delta-Ad) and likely the most effect vector for prostate cancer. We have made significant progress in the refinement of gutless Ad propagation. However, we will need continual improvement in this area. We will continue to improve on the blockade of transforming growth factor (TGF-beta) expression with new antisense constructs. Evaluation of tumor necrosis factor (TNF-alpha) related cytokine with less systemic toxicity is actively pursued as likely candidate for prostate cancer therapy.