Pharmaceutica Analytica Acta

Regression of prostate tumours following intravenous administration of tumour-targeted gene therapeutic systems

5^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 16-18, 2015 Crowne Plaza, Dubai, UAE

Majed Al Robaian, Ker Chiam Yi, David R Blatchford and Christine Dufes

Posters & Accepted Abstracts: Pharm Anal Acta

Abstract:

Cancer is a major public health problem worldwide. It is considered a major cause of death around the world. The World Health Organization estimates that 84 million people will die of cancer between 2005 and 2015, and the incidence is expected to increase continuously as the world population ages (Danhier et al., 2010). Prostate cancer pertains to the abnormal proliferation of cells of the prostate gland, resulting in the growth of the epithelial lining and eventual blockage of the urinary tract. To date, there is still no efficacious treatment for patients with advanced prostate cancer with metastases. New treatments are therefore critically needed for these patients. Gene therapy holds great promise for the intravenous treatment of prostate cancer. However, its use is currently limited by the lack of delivery systems able to selectively deliver therapeutic genes to tumours by intravenous administration. In our current study, we demonstrated that new tumour-targeted therapeutic systems recognizing receptors specifically overexpressed on prostate tumours, were able to improve the in vitro therapeutic efficacy on PC-3, DU145 and LNCaP prostate cancer cells when compared to the non-targeted delivery system, by up to 100-fold in LnCaP cells. In vivo, the intravenous administration of the tumour-targeted therapeutic system encoding Tumour Necrosis Factor (TNF) α resulted in tumour suppression for 60% of PC-3 and 50% of DU145 tumours. The dendriplex encoding TRAIL led to tumor suppression of 10% of PC-3 tumors. IL-12 mediated gene therapy resulted in tumor regression of 20% of both types of prostate tumors. By contrast, all the tumors treated with DAB-Tf, naked DNA or left untreated were progressive for both tumor types. The treatment was well tolerated by the animals, with no apparent signs of toxicity. These transferrin-bearing dendriplexes therefore hold great potential as a novel approach for the gene therapy of prostate cancer.