Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Portland Medical Center, USA.
Cancer J. 2011 Sep-Oct;17(5):379-96. doi: 10.1097/PPO.0b013e3182346320.
Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anticancer immune response in a patient with advanced cancer. But what is the evidence to support the "more-is-better" approach of multiple vaccinations? Because we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anticancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Because few large trials include immunologic monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at 1 or more times following the first vaccine, was performed. In some studies, there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings, multiple vaccinations can significantly reduce the immune response to 1 or more targets. Results from 3 large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the Food and Drug Administration approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies.
很少有免疫治疗师会接受单一疫苗接种就能在晚期癌症患者中诱导治疗性抗癌免疫反应的概念。但是，有什么证据支持多次接种的“多多益善”方法呢？由于我们不知道比较单一疫苗与多次接种对患者结局影响的试验，我们认为抗癌免疫反应可能是疫苗策略有效性的替代衡量指标。由于很少有大型试验包括免疫监测，因此大多数信息都是从小型试验中收集的，这些试验在首次接种疫苗前后 1 次或多次对疫苗或肿瘤的免疫反应进行了评估。在一些研究中，有令人信服的证据表明，重复给予特定疫苗可以增强疫苗中抗原的免疫反应。在其他情况下，多次接种会显著降低对 1 个或多个靶标的免疫反应。3 项大型佐剂疫苗研究的结果支持多次接种的潜在不利影响，因为对照组的临床结局明显优于治疗组。最近的研究提供了对上述研究中免疫反应降低的机制的深入了解，但通常缺乏来自临床标本的支持证据。这些结果的解释进一步复杂化，因为主导免疫反应可能进化为识别疫苗中不存在的表位。尽管如此，食品和药物管理局批准了首个治疗性癌症疫苗，以及来自临床前模型和临床试验的最新进展，为乐观和对癌症疫苗策略的批判性评估提供了坚实的基础。
