Cancer vaccines are entering a renaissance era due to an expanding knowledge immunoregulation and recent clinical trials with immunotherapies demonstrating therapeutic benefit. For example, Sipuleucel-T, an active immunotherapy product based on antigen-loaded GM-CSF activated peripheral blood mononuclear cells, has been shown to prolong survival in phase III trials in patients with advanced prostate cancer. Sipuleucel-T has recently been approved by the FDA for treatment of patients with metastatic prostate cancer thereby paving the regulatory path for the next generation of active immunotherapy products. While these first generation positive randomized phase III clinical trials need further analysis and mechanistic studies, they highlight the therapeutic potential of the immune-based treatments for solid tumors. We hypothesize that a novel dendritic cell (DC) vaccine will elicit long-lived T cell immunity able to control disease in patients with prostate cancer. We propose to test DCs generated by culturing monocytes with GM-CSF and type I interferon (IFN-DCs) and activated with LPS and CD40 ligand (CD40L). The antigenic cargo is composed of a mixture of long 25-35mer peptides from three prostate cancer (PrCa) antigens: PAP, PSA, and PSMA. The overall project is composed of two aims: Aim 1 will select the long peptides that will serve as the antigenic cargo of the IFN-DC vaccine. Aim 2 will be a pilot clinical trial in prostate cancer patients who have asymptomatic or minimally symptomatic castration resistant metastatic disease. The primary endpoint is vaccine immunogenicity at week 16. Thus, this project will establish a novel polyvalent vaccine for prostate cancer optimized for generation of CD8+ T cell immunity. Herein we request pilot funds that will allow us to gather preliminary results to support an R01 grant application that has been submitted to the NCI.