Journal Article

Evolving Role of Immunotherapy in Metastatic Castration Refractory Prostate Cancer

McFarland, Taylor Ryan, Nussenzveig, Roberto, Rathi, Nityam, Agarwal, Neeraj, Swami, Umang

2021

Overview

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.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Adenosine / Adenosine diphosphate / Age / Antigens / Apoptosis / Asymptomatic / Cancer therapies / Castration / Cell death / Chemotherapy / Clinical trials / Granulocytes / Immune checkpoint inhibitors / Immunotherapy / Inhibitors / Internal Medicine / Kinases / Leading / Leading Article / Lymphocytes / Lymphocytes T / Medicine / Medicine & Public Health / Metastases / Metastasis / Microsatellite instability / Mismatch repair / Monoclonal antibodies / Patients / Pharmacology/Toxicology / Pharmacotherapy / Poly(ADP-ribose) polymerase / Prostate cancer / Protein-tyrosine kinase / Radioisotopes / Ribose / Tumor microenvironment / Tumors / Tyrosine / Vaccines