Development of novel immune interventions for prostate cancer

Abstract

Prostate cancer is the leading cause of cancer-related morbidity and mortality in men in the Western world. Use of traditional and newer therapeutic regimens is constrained in terms of tolerance, efficacy, and cross-resistance. There is a need for newer therapies without overlapping mechanisms of action and toxicities to improve the outcome. Advances in the field of immunology and cancer biology have led to an improved understanding of the interactions between the immune system and tumors, propelling the field of cancer vaccines to the forefront of clinical investigation. Recent US Food and Drug Administration approval of sipuleucel-T, an autologous dendritic cell-based vaccine for the treatment of castration refractory prostate cancer, represents a significant advancement in the field of cancer vaccines. However, the overall survival benefits with sipuleucel-T are modest at best, and the field of cancer vaccine therapy is in a continuous state of evolution and expansion. Further improvements are expected to result from the selection of more appropriate tumor antigens, which circumvent immune tolerance, and from the development of more effective immunization strategies aimed at inducing an effective cytotoxic T-cell response. This review summarizes recent developments in the field of immunotherapy in prostate cancer with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, cell-based vaccines, peptide-based vaccine and therapies blocking immune checkpoints to break peripheral immune tolerance.