Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer

Dendritic cells or "DCs" are special white blood cells that stimulate the immune system. This study is being done to test the feasibility, safety and efficacy of a specific type of dendritic cell when injected under the skin of patients with prostate cancer. The researchers conducting this study will evaluate the time to prostate specific antigen (PSA) progression and will also be performing tests to see how the immune system is responding to the injections. This is a 2 group crossover trial in which patients are randomly assigned to one of two treatment arms: A. 3 months of androgen ablation (AA) to be followed at PSA progression by 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine (DC1); B. 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine followed at PSA progression by 3 months of AA. Primary Objectives * Feasibility objective: the ability to successfully generate and administer the alpha-DC1 vaccine. * Safety objective: assess the tolerability and toxicity of the alpha-DC1 vaccine. * Efficacy objective: evaluate the effect of the alpha-DC1 vaccine on time to PSA progression compared to AA alone. PSA progression is defined as a rise in the PSA value to e 1.0 ng/mL. Secondary Objectives * To determine the change in PSA velocity prior to and following the proposed treatment. * To evaluate (in all subjects) the vaccination-induced DTH responses to LNCap, the cell line vaccine, and to compare this with vaccination-induced responses to tumor-untreated antigen (KLH). * To evaluate the vaccination-induced changes of Th1/Th2 profiles of the responses to PAP and PSMA. * To evaluate the CTL responses in blood to the whole LNCap cells (in all subjects) and (in all subjects who are HLA-A2 positive) the CTL responses to HLA-A2.1 restricted peptides derived from PAP and PSMA. * To comprehensively evaluate the CD4+ and CD8+ T cell responses (fine specificity and Th1/Th2/Treg cytokine profile) to the previously-identified and novel immunogenic epitopes of PAP and PSMA, using the EPIMAX system. This is a 2 group crossover trial in which patients are randomly assigned to one of two treatment arms: A. 3 months of androgen ablation (AA) to be followed at PSA progression by 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine (DC1); B. 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine followed at PSA progression by 3 months of AA. In this crossover trial each patient will serve as their own control. Following either therapy the time to PSA progression, defined as the time between treatment and the first instance of PSA increase to 1ng/ml. The endpoint is the difference between time to PSA progression for the combination of AA + DC1 compared to AA alone. A total of 12 evaluable patients (6 patients/arm) will be enrolled on the trial. Patients who do not complete both courses (AA and AA+DCV) will be replaced. This schema will also help us better estimate the time to PSA recovery following 3 months of limited androgen ablation in our cohort of patients. All patients in Cohort B, will commence DC1-based vaccination 2 weeks prior to treatment with the LHRH analogue. Each patient will receive four i.d. doses of the vaccine at weeks 1, 4, 8, and 12. The LHRH analogue (Lupron 22.5 mg or Zoladex 10.8 mg), will be administered 2 weeks after the 1st dose of the DC vaccine. Additional courses of vaccination can be administered to any patients without evidence of disease progression, every 3 months for up to 12 months. Patients will undergo a thorough pre-study evaluation, and then undergo leukapheresis to generate the DC-based vaccine. Each patient will receive 4 doses of intradermal (i.d.) DC1-based vaccine at weeks 1, 4, 8, and 12.