Therapeutic cancer vaccines: are we there yet?
Therapeutic cancer vaccines: are we there yet?
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DOI：
10.1111/j.1600-065x.2010.00979.x
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发表时间：
2011-01
影响因子：
8.7
通讯作者：
Restifo NP
中科院分区：
文献类型：
--
作者：
Klebanoff CA;Acquavella N;Yu Z;Restifo NP
随着最近几项大型随机III期临床试验的完成，对治疗性癌症疫苗的热情重新焕发，在某些情况下，这些试验报告了无进展或总生存期的改善。然而，对其疗效的诚实评估显示其临床益处不大，并且经常需要用于相对惰性癌症和最小或无可测量疾病的患者。过继性细胞转移免疫疗法的经验明确表明，即使在晚期转移性疾病的情况下，T细胞也能介导持久的完全反应。此外，这些发现表明，未来成功的疫苗必须面对(i)含有调节性T细胞和异常成熟的骨髓细胞的腐败肿瘤微环境，（ii）易于免疫衰竭和衰老的肿瘤特异性T细胞库，以及（iii）具有抗原丢失和免疫逃避能力的高度可变肿瘤靶点。未来的进展可能来自于选择性制备方案的创新发展，以消除或中和抑制性细胞群，更有效的免疫佐剂，以及能够拮抗免疫检查点阻断途径的药物的进一步改进。
Enthusiasm for therapeutic cancer vaccines has been rejuvenated with the recent completion of several large, randomized phase III clinical trials that in some cases have reported an improvement in progression free or overall survival. However, an honest appraisal of their efficacy reveals modest clinical benefit and a frequent requirement for patients with relatively indolent cancers and minimal or no measurable disease. Experience with adoptive cell transfer-based immunotherapies unequivocally establishes that T cells can mediate durable complete responses, even in the setting of advanced metastatic disease. Further, these findings reveal that the successful vaccines of the future must confront (i) a corrupted tumor microenvironment containing regulatory T cells and aberrantly matured myeloid cells, (ii) a tumor-specific T-cell repertoire that is prone to immunologic exhaustion and senescence, and (iii) highly mutable tumor targets capable of antigen loss and immune evasion. Future progress may come from innovations in the development of selective preparative regimens that eliminate or neutralize suppressive cellular populations, more effective immunologic adjuvants, and further refinement of agents capable of antagonizing immune check-point blockade pathways.