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

SIMPLE SUMMARY: Prostate cancer is one of the most frequently diagnosed cancers amongst men worldwide. Treatment for metastatic disease is often in the form of androgen deprivation therapy. However, over the course of treatment affected men may become castrate-resistant. Options for men with metastatic castrate-resistant cancer are limited. This review focuses on the role of chimeric antigen receptor T-cell therapy (CAR-T) in men with metastatic castrate-resistant prostate cancer. This review is a contemporary appraisal of preclinical and clinical studies conducted in this emerging form of immunotherapy. A thorough evaluation of the role of CAR-T therapy in prostate cancer is provided, as well as the obstacles we must overcome to clinically translate this therapy for men affected with this rapidly fatal disease. 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.