Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive Suite 5726, Salt Lake City, UT, 84112, USA.
Drugs. 2021 Feb;81(2):191-206. doi: 10.1007/s40265-020-01456-z.
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.
免疫疗法在治疗多种癌症类型方面取得了显著的成功；然而，尽管在临床前研究中表现出令人鼓舞的活性，但免疫疗法在前列腺癌中的注册试验在很大程度上并未成功。基于总生存期的适度改善，Sipuleucel-T 仍然是唯一被批准用于治疗无症状或轻度症状转移性去势抵抗性前列腺癌的免疫疗法。这种前列腺癌中的免疫逃避归因于肿瘤内在因素、免疫抑制性肿瘤微环境和宿主因素，最终使肿瘤成为惰性的“冷”肿瘤。最近，已经研究了多种方法来使前列腺癌转变为“热”肿瘤。针对程序性细胞死亡蛋白 1 的抗体已被批准用于少数微卫星不稳定高或错配修复缺陷转移性前列腺癌患者，无论肿瘤类型如何。在此，我们概述了转移性去势抵抗性前列腺癌中免疫疗法的现状，重点介绍了免疫检查点抑制剂。我们描述了免疫检查点抑制剂在转移性去势抵抗性前列腺癌患者中的临床试验结果；无论是作为单一药物还是与其他检查点抑制剂、多聚（ADP-核糖）聚合酶（PARP）抑制剂、酪氨酸激酶抑制剂、新型激素疗法、化疗药物和放射性配体联合使用。最后，我们回顾了即将出现的免疫疗法，包括新型单克隆抗体、嵌合抗原受体（CAR）T 细胞、双特异性 T 细胞衔接器（BiTE）、针对腺苷途径的疗法以及其他各种药物。
