Prostate Cancer Immunotherapy: Time to Move Beyond Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have led the advancement of cancer immunotherapy, with remarkable efficacy in many cancers. Prior to the advent of ICIs, prostate cancer had one of the first approvals for cancer immunotherapy with sipleucel-T, an anti-cancer vaccine. Despite this early success, ICIs have since failed to improve outcomes for most patients with prostate cancer, generating a narrative that prostate cancer is resistant immunotherapeutic approaches. Novel therapies like CAR T-cells, bispecific antibody therapies, anti-cancer vaccines and cytokine therapies are now generating early evidence for how the prostate cancer tumor immune microenvironment can be manipulated beyond checkpoint inhibition. Most notably, clinical trials with bispecific T-cell engagers (BiTEs) targeting tumor antigens like STEAP-1 and KLK2 have shown clinical promise. Moving beyond ICIs may lead to new approaches to alter the prostate cancer tumor immune microenvironment and improve clinical outcomes.