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疫苗作为前列腺癌的治疗方法。

Vaccines as treatments for prostate cancer.

机构信息

University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI, USA.

出版信息

Nat Rev Urol. 2023 Sep;20(9):544-559. doi: 10.1038/s41585-023-00739-w. Epub 2023 Mar 6.

Abstract

Prostate cancer is a leading cause of death in men worldwide. For over 30 years, growing interest has focused on the development of vaccines as treatments for prostate cancer, with the goal of using vaccines to activate immune cells capable of targeting prostate cancer to either eradicate recurrent disease or at least delay disease progression. This interest has been prompted by the prevalence and long natural history of the disease and by the fact that the prostate is an expendable organ. Thus, an immune response elicited by vaccination might not need to target the tumour uniquely but could theoretically target any prostate tissue. To date, different vaccine approaches and targets for prostate cancer have been evaluated in clinical trials. Overall, five approaches have been assessed in randomized phase III trials and sipuleucel-T was approved as a treatment for metastatic castration-resistant prostate cancer, being the only vaccine approved to date by the FDA as a treatment for cancer. Most vaccine approaches showed safety and some evidence of immunological activity but had poor clinical activity when used as monotherapies. However, increased activity has been observed when these vaccines were used in combination with other immune-modulating therapies. This evidence suggests that, in the future, prostate cancer vaccines might be used to activate and expand tumour-specific T cells as part of combination approaches with agents that target tumour-associated immune mechanisms of resistance.

摘要

前列腺癌是全球男性死亡的主要原因之一。30 多年来,人们对疫苗作为前列腺癌治疗方法的开发越来越感兴趣,其目标是利用疫苗激活能够靶向前列腺癌的免疫细胞,要么根除复发性疾病,要么至少延缓疾病进展。这种兴趣源于该疾病的普遍性和较长的自然病史,以及前列腺是一个可消耗的器官这一事实。因此,疫苗引发的免疫反应可能不需要专门针对肿瘤,而理论上可以针对任何前列腺组织。迄今为止,已经在临床试验中评估了不同的前列腺癌疫苗方法和靶点。总体而言,已有五种方法在随机 III 期试验中进行了评估,sipuleucel-T 被批准用于治疗转移性去势抵抗性前列腺癌,是 FDA 迄今为止批准的唯一一种用于治疗癌症的疫苗。大多数疫苗方法显示出安全性和一些免疫活性的证据,但作为单一疗法的临床活性较差。然而,当这些疫苗与其他免疫调节疗法联合使用时,观察到了更高的活性。这一证据表明,未来前列腺癌疫苗可能被用于激活和扩增肿瘤特异性 T 细胞,作为联合治疗方案的一部分,联合针对肿瘤相关免疫耐药机制的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bebd/9987387/03ddf3c97c0a/41585_2023_739_Fig1_HTML.jpg

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