Vaccines for the Immunotherapy of Prostate Cancer

Abstract

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men in North America (1). Although locally confined disease is treatable, recurrent and metastasized prostate cancer is essentially incurable. Androgen ablation therapy often successfully, if temporarily, impacts the progression of advanced disease, as some prostate cancer cells are androgen-responsive (2–4). However, the majority of patients inevitably progress to incurable, androgen-independent disease (2,5– 8). In addition to the acquisition of hormone refractivity, tumor heterogeneity in prostate cancer is also a major problem in the clinical management of this disease. Prostate tumors have many different populations of cancer cells expressing a variety of tumor-associated antigens (TAAs). In addition, the progression of prostate cancer from the hormone-naive primary to an increasingly androgen-independent metastatic stage is associated with a number of molecular and genetic changes affecting the expression of specific TAAs on the cell surface. The challenge—not necessarily unique to prostate cancer—is that, in order to effectively treat the very heterogeneic prostate cancers, it is critical to identify novel markers and therapeutic targets in advanced prostate cancer and androgen-independent disease. Ideal targets for prostate cancer immunotherapy would include proteins that are: (a) highly expressed in metastatic prostate cancer cells; (b) not expressed, or expressed at very low level in normal tissues; (c) accessible to therapeutic modalities at the cancer cell surface; (d) not modulated by androgen. In the realm of prostate cancer, a number of promising immunotherapy targets have been identified, and are in various stages of preclinical development or clinical trials (9–17).KeywordsProstate CancerAdvanced Prostate CancerMetastatic Prostate CancerRecombinant Vaccinia VirusProstate Stem Cell AntigenThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.