New approaches to therapeutics of advanced prostate cancer are urgently needed. GVAX (granulocyte-macrophage colony-stimulating factor [GM-CSF] gene transduced irradiated prostate cancer vaccine cells) offers the possibility that "host versus prostate cancer" immune responses can be generated in prostate cancer patients. Critical components involve the dendritic cell loading of candidate prostate cancer lymph node metastasis and candidate bone metastasis antigens derived from irradiated prostate cancer whole cells. GM-CSF acts at the vaccination site to enhance activation dendritic cells and antigen presentation to both the B-cell and T-cell arms of the immune system. GVAX preclinically-in both rat and transgenic prostate cancer models-has antitumor activity which has informed early clinical trial designs. Clinical investigations reviewed in this report suggest that vaccination is safe and immune tolerance can be broken against prostate cancer. Multi-institutional phase III investigation is currently underway to evaluate the impact of allogeneic prostate GVAX cellular immunotherapy on time to progression and overall survival in hormone refractory prostate cancer.