Abstract
Prostate cancer (PCa) has a vast clinical spectrum from the hormone-sensitive setting to castration-resistant metastatic disease. Thus, chemotherapy regimens and the administration of androgen receptor axis-targeted (ARAT) agents for advanced PCa have shown limited therapeutic efficacy. Scientific advances in the field of molecular medicine and technological developments over the last decade have paved the path for immunotherapy to become an essential clinical modality for the treatment of patients with metastatic PCa. However, several immunotherapeutic agents have shown poor outcomes in patients with advanced disease, possibly due to the low PCa mutational burden. Adoptive cellular approaches utilizing chimeric antigen receptor T cells (CAR-T) targeting cancer-specific antigens would be a solution for circumventing the immune tolerance mechanisms. The immunotherapeutic regimen of CAR-T cell therapy has shown potential in the eradication of hematologic malignancies, and current clinical objectives maintain the equivalent efficacy in the treatment of solid tumors, including PCa. This review will explore the current modalities of CAR-T therapy in the disease spectrum of PCa while describing key limitations of this immunotherapeutic approach and discuss future directions in the application of immunotherapy for the treatment of metastatic PCa and patients with advanced disease.
Highlights
Estimates have shown that the mortality rate of metastatic castration-resistant prostate cancer and the fatal manifestation of the disease are approximately 31,000 cases annually [1]
The study results showed a PSA were crossed with human leucocyte antigen (HLA)-A2.1-expressing mice to analyze the effects of androgen deprivation on T cells
The study results showed a substantial increase in cytotoxic lymphocytes specific to PSA, especially in the setting of androgen ablation [33]
Summary
Estimates have shown that the mortality rate of metastatic castration-resistant prostate cancer (mCRPC) and the fatal manifestation of the disease are approximately 31,000 cases annually [1]. In the PCa treatment setting, CAR-T cells targeting PSMA have displayed encouraging results, suggesting a potential translational treatment target for the treatment of PCa in the advanced clinical setting [6]. These clinical outcomes will open new horizons in the treatment and cure for the disease continuum of PCa. This article provides a thorough overview of the role of CAR-T cell therapy in advanced PCa and the metastatic setting will be provided along with an extensive review of current and future modalities that will further improve the therapeutic spectrum in the ongoing treatment of advanced PCa and metastatic disease
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