Yeku Oladapo, Slovin Susan F
From the Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY.
Cancer J. 2016 Sep/Oct;22(5):334-341. doi: 10.1097/PPO.0000000000000223.
Immunotherapy for castration-resistant prostate cancer has continued to be an area of active research over the last several years. The enthusiasm of this approach has been based on the assumption of better tolerability and that using the body's own immune system may be more effective than either hormonal or chemotherapy. Sipuleucel-T, a dendritic cell-based vaccine, is the only approved agent in this class for the management of castrate-resistant prostate cancer. Although sipuleucel-T increases overall survival without any significant changes in progression-free survival, other forms of immunotherapy such as PSA-TRICOM, ipilimumab, and chimeric antigen receptor T cell therapy are in advanced stages of clinical development. Immune biomarkers are being developed to assess response to these treatments and also to understand how the immune system responds to these respective therapies. Combinations of immunotherapy with androgen deprivation, radiation therapy, and chemotherapy have also been explored with varying results. This review discusses the mechanisms, key preclinical and clinical data, and perspectives for immunotherapeutic agents in the treatment scheme for castrate-resistant prostate cancer.
在过去几年中，去势抵抗性前列腺癌的免疫疗法一直是一个活跃的研究领域。这种方法之所以受到关注，是基于其耐受性较好的假设，以及利用人体自身免疫系统可能比激素疗法或化疗更有效的观点。西妥昔单抗-T（Sipuleucel-T），一种基于树突状细胞的疫苗，是此类中唯一被批准用于治疗去势抵抗性前列腺癌的药物。尽管西妥昔单抗-T可提高总生存率，且无进展生存期无显著变化，但其他形式的免疫疗法，如PSA-TRICOM、伊匹单抗和嵌合抗原受体T细胞疗法，正处于临床开发的后期阶段。正在开发免疫生物标志物，以评估对这些治疗的反应，并了解免疫系统对这些各自疗法的反应。免疫疗法与雄激素剥夺、放射疗法和化疗的联合应用也已进行了探索，结果各异。本综述讨论了免疫治疗药物在去势抵抗性前列腺癌治疗方案中的作用机制、关键的临床前和临床数据以及前景。
