Morse Michael A, Chui Stephen, Hobeika Amy, Lyerly H Kim, Clay Timothy
Duke University Medical Center, Durham, North Carolina 27710, USA.
Nat Clin Pract Oncol. 2005 Feb;2(2):108-13. doi: 10.1038/ncponc0098.
Therapeutic cancer vaccines are being developed with the intention of treating existing tumors or preventing tumor recurrence. While the results of clinical trials, predominantly in the metastatic setting have been sobering, the central hypothesis of active immunotherapy i.e. that the human immune system can be activated to recognize and destroy tumor cells, remains a viable one. We believe that a fundamental shift in how clinical trials are performed, and what concepts they test is required to make meaningful strides towards future clinical use of cancer vaccines. First, we must reappraise whether the metastatic setting is the appropriate arena to test these agents. Second, we must arrive at a consensus on the most important biologic endpoints and rapidly test vaccines for their ability to achieve these endpoints. Third, we need to expend more effort on understanding how to manipulate the immune system beyond the initial stimulation provided by a vaccine. Fourth, in order to permit comparison of results across different studies, it would be helpful to narrow down the large number of vaccine platforms. We will discuss the current state of development of cancer vaccines and the relevance for future clinical use of these agents to treat and prevent cancers.
治疗性癌症疫苗正在研发中,旨在治疗现有肿瘤或预防肿瘤复发。虽然主要在转移性环境中的临床试验结果令人沮丧,但主动免疫疗法的核心假设,即人类免疫系统可以被激活以识别和摧毁肿瘤细胞,仍然是可行的。我们认为,在癌症疫苗的未来临床应用方面取得有意义的进展,需要在临床试验的进行方式以及所测试的概念上进行根本性转变。首先,我们必须重新评估转移性环境是否是测试这些药物的合适场所。其次,我们必须就最重要的生物学终点达成共识,并迅速测试疫苗实现这些终点的能力。第三,我们需要投入更多精力来理解如何在疫苗提供的初始刺激之外操纵免疫系统。第四,为了便于比较不同研究的结果,缩小大量疫苗平台的范围将有所帮助。我们将讨论癌症疫苗的当前发展状况以及这些药物在未来临床治疗和预防癌症中的相关性。