Abstract 3368: Efficient delivery of prostate cancer gene therapy via adipose-derived mesenchymal stem cells in vivo

Abstract

Abstract It is critical to develop new therapeutic approaches for prostate cancer, since there is no effective treatment for patients in the advanced stages of this disease. And although many gene therapy approaches have been evaluated to date, clinical responses unfortunately remain poor. We have examined the potential of developing more effective cell-based gene therapies for preventing prostate cancer progression, using adipose-derived mesenchymal stem cells (ASC) as vehicles. The present study reports promising preliminary observations using this novel gene therapy modality. ASCs can be isolated using simpler methods as compared to those involving bone marrow mesenchymal cells, and are much more easily expanded at early passage numbers to therapeutic quantities. And since current techniques allow isolation of ASCs from an individual's own adipose tissue, this could help prevent immune reaction, suggesting that ASCs could be far more efficient as a gene delivery vehicle than viral vectors currently in clinical trials. In this study we have examined the potential of new antiangiogenesis and proapoptotic therapies delivered by ASCs and evaluated their ability to reduce prostate tumor growth rate in vitro and in vivo. We expressed in ASCs several secreted antitumor gene therapies (PEDF, Mda7, or IFNb), and all were found to be highly effective in almost complete prevention of tumor progression in vivo using prostate cancer xenograft models. Overall, ASC-delivered PEDF prevented HUVEC tube formation in vitro and induced strong apoptosis of cocultured cancer cells, suggesting a potential bystander effect that might be useful for therapeutic applications. Similar antitumor findings were observed when Mda7 or IFNb were delivered by ASCs, with induction of strong cell cycle arrest, and viability reduction by an increase in the apoptosis of cocultured tumor cells as assessed by Caspase 3/7 detection. The transgene expression was overall non-toxic and did not appear to interfere with the normal differentiation potential of ASCs (osteogenesis or adipogenesis). Therefore, this novel cellular delivery method for gene therapy appears to be effective and highly promising for translational applications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3368. doi:1538-7445.AM2012-3368