Update: Immunological Strategies for Prostate Cancer

Prostate cancer is the second most common cause of cancer-related death in US men. Along with initial therapy using surgery, radiotherapy, or cryotherapy, hormonal therapy is the mainstay of treatment. For men with advanced (metastatic) disease, docetaxel-based chemotherapy is US Food and Drug Administration (FDA)-approved, and provides a significant survival advantage. This relative paucity of treatment options drives an ongoing quest for additional treatment modalities; among these is immunotherapy. The concept that prostate cancer is a malignancy that can be targeted by the immune system may seem counterintuitive; certainly kidney cancer and melanoma are more traditionally thought of as immune responsive cancers. However, prostate cancer arises in a relatively unique organ and may express a number of proteins (antigens) against which an immune response can be generated. More importantly, several of these agents have now demonstrated a significant survival benefit in randomized controlled clinical trials, and one agent in particular (Sipuleucel-T, Dendreon Corporation, Seattle, WA) could be FDA-approved in 2010. This update summarizes recent clinical developments in the field of prostate cancer immunotherapy, with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, and cell-based vaccines. In addition, the notion of agents that target immune checkpoints is introduced. Enthusiasm for prostate cancer immunotherapy is founded upon its potential to mediate targeted, specific, tumor cell destruction without significant systemic toxicity; however, this has yet to be fully realized in the clinical arena.