Ogi Chizuru, Aruga Atsushi
Cooperative Major in Advanced Biomedical Sciences; Joint Graduate School of Tokyo Women's Medical University and Waseda University; Tokyo, Japan.
Oncoimmunology. 2013 Aug 1;2(8):e26012. doi: 10.4161/onci.26012. Epub 2013 Aug 23.
Therapeutic anticancer vaccines operate by eliciting or enhancing an immune response that specifically targets tumor-associated antigens. Although intense efforts have been made for developing clinically useful anticancer vaccines, only a few Phase III clinical trials testing this immunotherapeutic strategy have achieved their primary endpoint. Here, we report the results of a retrospective research aimed at clarifying the design of previously completed Phase II/III clinical trials testing therapeutic anticancer vaccines and at assessing the value of immunological monitoring in this setting. We identified 17 anticancer vaccines that have been investigated in the context of a completed Phase II/III clinical trial. The immune response of patients receiving anticancer vaccination was assessed for only 8 of these products (in 15 distinct studies) in the attempt to identify a correlation with clinical outcome. Of these studies, 13 were supported by a statistical correlation study (Log-rank test), and no less than 12 identified a positive correlation between vaccine-elicited immune responses and disease outcome. Six trials also performed a Cox proportional hazards analysis, invariably demonstrating that vaccine-elicited immune responses have a positive prognostic value. However, despite these positive results in the course of early clinical development, most therapeutic vaccines tested so far failed to provide any clinical benefit to cancer patients in Phase II/III studies. Our research indicates that evaluating the immunological profile of patients at enrollment might constitute a key approach often neglected in these studies. Such an immunological monitoring should be based not only on peripheral blood samples but also on bioptic specimens, whenever possible. The evaluation of the immunological profile of cancer patients enrolled in early clinical trials will allow for the identification of individuals who have the highest chances to benefit from anticancer vaccination, thus favoring the rational design of Phase II and Phase III studies. This approach will undoubtedly accelerate the clinical development of therapeutic anticancer vaccines.
治疗性抗癌疫苗通过引发或增强针对肿瘤相关抗原的免疫反应来发挥作用。尽管在开发临床上有用的抗癌疫苗方面已经付出了巨大努力，但只有少数测试这种免疫治疗策略的III期临床试验达到了其主要终点。在此，我们报告一项回顾性研究的结果，该研究旨在阐明先前完成的测试治疗性抗癌疫苗的II/III期临床试验的设计，并评估在这种情况下免疫监测的价值。我们确定了17种已在完成的II/III期临床试验中进行研究的抗癌疫苗。在这些产品中，仅对其中8种（在15项不同研究中）接受抗癌疫苗接种的患者的免疫反应进行了评估，以试图确定与临床结果的相关性。在这些研究中，13项得到了统计相关性研究（对数秩检验）的支持，并且不少于12项研究确定了疫苗引发的免疫反应与疾病结果之间存在正相关。六项试验还进行了Cox比例风险分析，均表明疫苗引发的免疫反应具有积极的预后价值。然而，尽管在早期临床开发过程中取得了这些积极结果，但到目前为止，大多数测试的治疗性疫苗在II/III期研究中未能为癌症患者提供任何临床益处。我们的研究表明，在入组时评估患者的免疫特征可能是这些研究中经常被忽视的关键方法。这种免疫监测不仅应基于外周血样本，而且在可能的情况下还应基于活检标本。对参与早期临床试验的癌症患者的免疫特征进行评估将有助于识别最有可能从抗癌疫苗接种中受益的个体，从而有利于II期和III期研究的合理设计。这种方法无疑将加速治疗性抗癌疫苗的临床开发。
