[HTML][HTML] Evolving role of immunotherapy in metastatic castration refractory prostate cancer

N Rathi, TR McFarland, R Nussenzveig, N Agarwal… - Drugs, 2021 - Springer
Drugs, 2021Springer
Immunotherapies have shown remarkable success in the treatment of multiple cancer types;
however, despite encouraging preclinical activity, registration trials of immunotherapy in
prostate cancer have largely been unsuccessful. Sipuleucel-T remains the only approved
immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic
castrate-resistant prostate cancer based on modest improvement in overall survival. This
immune evasion in the case of prostate cancer has been attributed to tumor-intrinsic factors …
Abstract
Immunotherapies have shown remarkable success in the treatment of multiple cancer types; however, despite encouraging preclinical activity, registration trials of immunotherapy in prostate cancer have largely been unsuccessful. Sipuleucel-T remains the only approved immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer based on modest improvement in overall survival. This immune evasion in the case of prostate cancer has been attributed to tumor-intrinsic factors, an immunosuppressive tumor microenvironment, and host factors, which ultimately make it an inert ‘cold’ tumor. Recently, multiple approaches have been investigated to turn prostate cancer into a ‘hot’ tumor. Antibodies directed against programmed cell death protein 1 have a tumor agnostic approval for a small minority of patients with microsatellite instability-high or mismatch repair-deficient metastatic prostate cancer. Herein, we present an overview of the current immunotherapy landscape in metastatic castration-resistant prostate cancer with a focus on immune checkpoint inhibitors. We describe the results of clinical trials of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer; either as single agents or in combination with other checkpoint inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, tyrosine kinase inhibitors, novel hormonal therapies, chemotherapies, and radioligands. Finally, we review upcoming immunotherapies, including novel monoclonal antibodies, chimeric-antigen receptor (CAR) T cells, Bi-Specific T cell Engagers (BiTEs), therapies targeting the adenosine pathway, and other miscellaneous agents.
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