Activation and Protection of Dendritic Cells in the Prostate Cancer Environment

Abstract

Abstract : Fourth annual report for this award. Experiments were conducted as was scheduled in the Statement of Work. In vivo experiments were carried out, in which mice with prostate cancer (RM-1 cells) were treated with modified dendritic cells (DC). These cells were treated TNFa and ETB receptor inhibitor. Unlike experiments performed in previous years of this award, DC were delivered not intratumorally, but in subcutaneously in the flank opposite to the tumor injection side. Because of that, these DC were stimulated with RM-1 cells lysates, to provide target antigen for DC. Translating to human population, if these experiments are successful, they should provide the ability to treat patients who have no easily injectable tumor site. This treatment resulted in reduction of prostate cancer growth in mice in the experimental group, in comparison to untreated control mice. No statistically significant difference was found due to low number of treated mice, but more experiments are scheduled. RNA was extracted from different cells (murine prostate, murine prostate cancer cells, dendritic cells after different stimulation), and comparison gene arrays are underway. We hope that these arrays will provide us with directions for further more detailed studies to elucidate the mechanisms of prostate cancer-induced apoptosis of DC, and the role of endothelin receptors in the functioning of dendritic cells.