Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach

Cell Rep Med. 2023 Oct 17;4(10):101199. doi: 10.1016/j.xcrm.2023.101199. Epub 2023 Sep 21.

Abstract

Cancer immunotherapy has gained traction in recent years owing to remarkable tumor clearance in some patients. Despite the notable success of immune checkpoint blockade (ICB) in multiple malignancies, engagement of the immune system for targeted prostate cancer (PCa) therapy is still in its infancy. Multiple factors contribute to limited response, including the heterogeneity of PCa, the cold tumor microenvironment, and a low number of neoantigens. Significant effort is being invested in improving immune-based PCa therapies. This review is a summary of the status of immunotherapy in treating PCa, with a discussion of multiple immune modalities, including vaccines, adoptively transferred T cells, and bispecific T cell engagers, some of which are undergoing clinical trials. In addition, this review also focuses on emerging mechanism-based small-molecule tyrosine kinase inhibitors with immune modulatory properties that, either as single agents or in combination with other immunotherapies, have the potential to improve clinical outcomes.

Keywords: (R)-9b; AR; BiTE; CAR T cell therapy; CEP-11981; CRPC; CTC; ICB; SGI-9481; TKI; androgen receptor; cabozantinib; castration-resistant prostate cancer; ibrutinib; immune checkpoint blockade; pexidartinib; prostate cancer; small-molecule inhibitors; vaccine.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Humans
  • Immunotherapy
  • Male
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / pathology
  • T-Lymphocytes / pathology
  • Tumor Microenvironment