Past, Current, and Future of Immunotherapies for Prostate Cancer

Abstract

Prostate cancer (PCa) is the most common cancer in men, and the second leading cause of cancer related death in men in Western countries. The standard therapy for metastatic PCa is androgen suppression therapy (AST). Men undergoing AST eventually develop metastatic castration-resistant prostate cancer (mCRPC), of which there are limited treatment options available. Immunotherapy has presented substantial benefits for many types of cancer, but only a marginal benefit for mCRPC, at least in part, due to the immunosuppressive tumor microenvironment (TME). Current clinical trials are investigating monotherapies or combination therapies involving adoptive cellular therapy, viral, DNA vaccines, oncolytic viruses, and immune checkpoint inhibitors (ICI). Immunotherapies are also being combined with chemotherapy, radiation, and AST. Additionally, preclinical investigations show promise with the recent description of alternative ways to circumvent the immunosuppressive nature of the prostate tumor microenvironment, including harnessing the immune stimulatory NKG2D pathway, inhibiting myeloid derived suppressor cells, and utilizing immunomodulatory oncolytic viruses. Herein we provide an overview of recent preclinical and clinical developments in cancer immunotherapies and discuss the perspectives for future immunotherapies in PCa.

Keywords: combination therapy; immune checkpoint inhibitor; immunotherapy; metastatic-castration resistant prostate cancer; prostate cancer.

Figure 1

Snapshot of clinical trials ongoing for prostate cancer in 2019. (A) As of May 2019, a total of 1,195 clinical trials were ongoing for prostate cancer, with 12% of these trials involving at least one immunotherapeutic. (B) Of the ongoing immunotherapeutic trials, two are in early Phase, 46 are in Phase I, 84 are in Phase II, and seven are in Phase III. Approximately half of the ongoing trials are testing combination therapies with two or more therapeutics. (C) PD-1/PD-L1 blockade, CLTA-4 blockade, AST, and Sip-T are implemented in combination clinical trials with a variety of different therapies.