Chimeric Antigen Receptor T-Cell Therapy in Metastatic Castrate-Resistant Prostate Cancer

Abstract

Prostate cancer is the most commonly diagnosed solid-organ cancer amongst males worldwide. Metastatic castrate-resistant prostate cancer (mCRPC) is a rapidly fatal end-sequelae of prostate cancer. Therapeutic options for men with mCRPC are limited and are not curative in nature. The recent development of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the treatment of treatment-resistant haematological malignancies, and several studies are underway investigating the utility of this technology in the treatment of solid tumours. In this review, we evaluate the current treatment options for men with mCRPC as well as the current landscape of preclinical and clinical trials of CAR-T cell therapy against prostate cancer. We also appraise the various prostate cancer-specific tumour-associated antigens that may be targeted by CAR-T cell technology. Finally, we examine the potential translational barriers of CAR-T cell therapy in solid tumours. Despite preclinical success, preliminary clinical trials in men with prostate cancer have had limited efficacy. Therefore, further clinically translatable preclinical models are required to enhance the understanding of the role of this investigational therapeutic in men with mCRPC. In the era of precision medicine, tailored immunotherapy administered to men in a tumour-agnostic approach provides hope to a group of men who otherwise have few treatment options available.

Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease

“…The process begins from T-cell collection through leukapheresis. T cells are genetically altered to express CAR which can target tumor-associated antigens (TAA) [ 106 ]. Lymphodepletion is usually performed before injection, which can cause CAR-T cells lymphopenia and more suitable to the tumor microenvironment [ 107 ].…”

“…Lymphodepletion is usually performed before injection, which can cause CAR-T cells lymphopenia and more suitable to the tumor microenvironment [ 107 ]. Finally, purified CAR-T cells are administrated back to patients [ 106 ] ( Figure 1 ). Different strategies are developed to create CAR-T cells.…”

“…Three patients of the second cohort developed mild cytokine release syndrome that was self-resolving [ 111 ]. Based on this outcome, many clinical trials of anti-PSMA CART-T cells are underway [ 105 , 106 ]. P-PSMA-101 CAR-T cells are autologous purified CART-T cells developed through a novel technique.…”

Signaling Pathways and Targeted Therapies for Stem Cells in Prostate Cancer

“…171 Investigations are still being conducted to discover novel tumor specific antigens to overcome the immunosuppressive nature of the tumor microenvironment (TME) and the heterogeneous population of the TME. 172…”

“…A study conducted by Feldmann et al used PSMA-specific CAR T cells coexpressing PSCA-specific receptors to kill both subsets of PCa cells . Investigations are still being conducted to discover novel tumor specific antigens to overcome the immunosuppressive nature of the tumor microenvironment (TME) and the heterogeneous population of the TME …”