Pitfalls or Promise in Prostate Cancer Immunotherapy—Which Is Winning?

Abstract

Immunotherapy with vaccines, cytokines, and monoclonal antibodies against checkpoint molecules has been introduced into the clinical arena. Although all have demonstrated safety in clinical trials in patients with castrate metastatic prostate cancer, no one approach has been able to provide improved overall survival. This article is a review of the current issues and potential resolutions as to how we might go forward in developing and interpreting immunologic trials. Phase I, II, and III trials showed that immunologic tolerance can be abrogated against specific tumor-associated antigens, but the immunologic readouts are suboptimal in determining whether a trial can go forward in its development. Combinatorial approaches appear to be necessary for inducing immunogenicity and antitumor effects. Strategies include irradiated tumor cells lines, costimulatory molecules, or immune checkpoint inhibitors, which are in trials and are under intense scrutiny as to their impact on clinical end points such as time to disease progression and survival. Strategies to enhance immunogenicity of vaccines and reassess how to effectively establish interpretable immunologic end points are under development and appear to be successful in affecting how these trials go forward.