Demystifying immunotherapy in prostate cancer: understanding current and future treatment strategies.
Demystifying immunotherapy in prostate cancer: understanding current and future treatment strategies.
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DOI：
10.1097/ppo.0b013e31828160a9
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Kantoff PW
中科院分区：
文献类型：
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作者：
Madan RA;Gulley JL;Kantoff PW
免疫疗法已成为前列腺癌患者的一种可行的治疗选择。有多种采用免疫系统的潜在策略，包括设计用于刺激免疫细胞靶向癌细胞表达的抗原的治疗性癌症疫苗。Sipuleucel-T是目前批准用于治疗症状轻微的转移性前列腺癌的疫苗，而疫苗PSA-TRICOM和免疫检查点抑制剂ipilimumab正在进行III期测试。尽管疾病进展或可用生物标志物评估反应没有短期变化，但这些药物似乎改善了生存率。一种假设表明，这种明显的悖论可以通过这些治疗的生长调节作用来解释，这些治疗不会导致肿瘤尺寸缩小，而是随着时间的推移停止或减缓其生长速度。出于这个原因，正在研究在疾病过程的早期使用免疫疗法。另一种方法是阻断由分子CTLA-4和PD-1介导的免疫调节机制。其他未来策略将联合收割机免疫疗法与其他标准疗法相结合，可能增强后者的临床影响，从而改善进展时间和总生存率，因为这两种治疗的联合作用。前瞻性试验目前正在评估这些假设，并将最终用于优化前列腺癌治疗中的免疫疗法。
Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that employ the immune system including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, while the vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth moderating effects of these treatments which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune regulatory mechanisms mediated by the molecules CTLA-4 and PD-1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter’s clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer.