Novel immunotherapies for prostate cancer

Since the advent of the autologous dendritic cell-based vaccine, sipuleucel-T, in 2010, the clinical development of immunotherapeutic approaches in advanced prostate cancer has largely been lacking. Aside from the infrequent use of pembrolizumab immune checkpoint blockade in rare molecularly-selected patients, no further immune approaches have achieved regulatory approval. Numerous challenges exist that preclude successful clinical development, including an immunologically-excluded tumor immune microenvironment, off-target and/or inflammatory toxicities that narrow the therapeutic window, and limited durability of anti-tumor responses. Nevertheless, recent advances in drug design and cellular engineering have reinvigorated interest in novel immunotherapeutic approaches in prostate cancer. This review provides an overview of the current landscape of novel immunotherapy clinical development for prostate cancer, with a focus on chimeric antigen receptor (CAR) T cells, T cell engagers, monoclonal antibodies, and cancer vaccine approaches that have produced promising early phase clinical data.