Vaccines as treatments for prostate cancer

Prostate cancer is a leading cause of death in men worldwide. For over 30 years, growing interest has focused on the development of vaccines as treatments for prostate cancer, with the goal of using vaccines to activate immune cells capable of targeting prostate cancer to either eradicate recurrent disease or at least delay disease progression. This interest has been prompted by the prevalence and long natural history of the disease and by the fact that the prostate is an expendable organ. Thus, an immune response elicited by vaccination might not need to target the tumour uniquely but could theoretically target any prostate tissue. To date, different vaccine approaches and targets for prostate cancer have been evaluated in clinical trials. Overall, five approaches have been assessed in randomized phase III trials and sipuleucel-T was approved as a treatment for metastatic castration-resistant prostate cancer, being the only vaccine approved to date by the FDA as a treatment for cancer. Most vaccine approaches showed safety and some evidence of immunological activity but had poor clinical activity when used as monotherapies. However, increased activity has been observed when these vaccines were used in combination with other immune-modulating therapies. This evidence suggests that, in the future, prostate cancer vaccines might be used to activate and expand tumour-specific T cells as part of combination approaches with agents that target tumour-associated immune mechanisms of resistance. In this Review, current vaccine-based approaches to treat prostate cancer are described. The authors discuss results from clinical trials in which overall vaccine safety and biological activity were shown, albeit with modest clinical activity, suggesting that the future of these approaches will be as part of combination therapies with agents targeting tumour-associated immune mechanisms of resistance. Key points Over 175 clinical trials to assess antitumour vaccines as treatments for prostate cancer have been conducted over the past 30 years. A total of five vaccine approaches have been evaluated in randomized phase III trials. One vaccine approach, sipuleucel-T, has been approved by the FDA as a treatment for advanced prostate cancer. Most vaccine approaches showed safety and biological activity, yet little clinical activity was observed when these vaccines were used as monotherapies. Future exploration of prostate cancer vaccines will focus on the use of these agents to