Schlom Jeffrey, Arlen Philip M, Gulley James L
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Clin Cancer Res. 2007 Jul 1;13(13):3776-82. doi: 10.1158/1078-0432.CCR-07-0588.
The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. Although no therapeutic cancer vaccine has to date been approved by the Food and Drug Administration, several new paradigms are emerging from recent clinical findings both in the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and end point analyses. This article will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classic "tumor response" (Response Evaluation Criteria in Solid Tumors) criteria with "patient response" in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with "conventional" combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell--mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies.
癌症疫苗领域目前正处于临床前和临床研究的活跃状态。尽管迄今为止尚无治疗性癌症疫苗获得美国食品药品监督管理局的批准，但从近期的临床研究结果中正在涌现出几种新的模式，这些模式既体现在联合治疗方法的使用上，或许更重要的是，体现在临床试验设计和终点分析方面。本文将回顾近期涉及几种不同癌症疫苗的临床试验，从这些试验中得出的数据将经典的“肿瘤反应”（实体瘤疗效评价标准）标准与疫苗治疗后患者生存率提高这一表现中的“患者反应”进行了对比。还描述了几种癌症疫苗可与其他药物和治疗方式联合使用的策略，与“传统”联合疗法相比，这些策略相当独特。这很可能是由于以下现象：（a）癌症疫苗引发了一种动态免疫过程，可在后续治疗中加以利用；（b）放疗和某些化疗药物已被证明可改变肿瘤细胞的表型，使其更易受到T细胞介导的杀伤。因此，几项研究正在出现证据，表明与对照组相比，首先接受癌症疫苗接种的患者队列在临床上从后续治疗中获益。
