Vaccine and Antibody Treatment of Prostate Cancer

Background: * Adenocarcinoma of the prostate is the most common cancer diagnosis in American males, and the second leading cause of cancer death. * The proposed vaccine strategy represents a third-generation design that elicits a T-cell immune response to cells expressing PSA and has been shown to break tolerance to this self-antigen, and cause objective response and PSA declines in patients with metastatic AIPC. * This strategy also utilizes an antibody to CTLA-4 that may block the normal signals to down regulate the immune response following active vaccination. * Anti CTLA-4 antibodies have been associated with autoimmune events that are generally manageable and have been associated with clinical response. Objectives: * To determine the safety and tolerability of a combination of a fixed dose of vaccine and anti-CTLA4, which will be dose escalated. * To evaluate immunologic response (as measured by an increase in PSA specific T-cells measured by ELISPOT in HLA-A2+ patients), and clinical response (as measured by RECIST and PSA consensus criteria). Eligibility: * Must have metastatic androgen insensitive prostate cancer with no bone pain requiring narcotics and have had no more prior chemotherapy. * Life expectancy greater than or equal to 6 months. ECOG 0-1 * Should have no autoimmune diseases; no evidence of being immunocompromised; no serious intercurrent medical illness; no cardiac disease; no prior splenectomy. * No prior treatment with MDX-010 (Ipilimumab). * No brain metastasis, history of seizures, encephalitis, or multiple sclerosis. * No serious hypersensitivity reaction to egg products. Design: * This is an open label, phase I safety trial with sequential cohorts of patients all receiving a fixed dose of PSA-TRICOM vaccines and sargramostim, with dose escalation of MDX-010 (Ipilimumab). * PROSTVAC -V/TRICOM (vaccinia) 2 x 10(8) pfu subcutaneously will be administered as the initial priming vaccine on day 1 of cycle 1 only. * PROSTVAC -F/TRICOM (fowlpox) 1 x 10(9) pfu subcutaneously starting on day 15 followed by monthly boosting vaccination. Sargramostim 100 mcg per day will be administered subcutaneously at the vaccination site on days 1-4 of each vaccine cycle (prime and boost). * MDX-010 (Ipilimumab) will be administered, as per the assigned dose level, as a 90-minute intravenous infusion on the same day as the monthly boosting vaccinations with PROSTVAC-F/TRICOM (fowlpox). After 6 courses of MDX-010, patients may receive Maintenance dose of MDX-010 every 3 months until there is evidence of disease progression or toxicity, for up to an additional 12 months (equivalent to 4 additional MDX-010 courses). * Monthly boosting vaccinations with PROSTVAC-F/TRICOM (fowlpox) and sargramostim may then continue until patients meet off study criteria.