Schlom Jeffrey, Gulley James L, Arlen Philip M
Laboratory of Tumor Immunology and Biology, CCR, NCI, 10 Center Drive, Room 8B09, Bethesda, MD 20892, USA.
Exp Biol Med (Maywood). 2008 May;233(5):522-34. doi: 10.3181/0708-MR-226. Epub 2008 Mar 28.
Cancer vaccines constitute a unique therapeutic modality in that they initiate a dynamic process involving the host's immune response. Consequently, (a) repeated doses (vaccinations) over months may be required before patient clinical benefit is observed and (b) there most likely will be a "dynamic balance" between the induction and maintenance of host immune response elements to the vaccinations vs. host/tumor factors that have the potential to diminish those responses. Thus "patient response" in the form of disease stabilization and prolonged survival may be more appropriate to monitor than strictly adhering to "tumor response" in the form of Response Criteria In Solid Tumors (RECIST) criteria. This can be manifested in the form of enhanced patient benefit to subsequent therapies following vaccine therapy. This article will review these phenomena unique to cancer vaccines with emphasis on prostate cancer vaccines as a prototype for vaccine therapy. The unique features of this modality require the consideration of paradigm shifts both in the way cancer vaccine clinical trials are designed and in the way patient benefit is evaluated.
癌症疫苗构成了一种独特的治疗方式，因为它们启动了一个涉及宿主免疫反应的动态过程。因此，（a）在观察到患者临床获益之前，可能需要在数月内重复给药（接种疫苗）；（b）在针对疫苗接种诱导和维持宿主免疫反应成分与可能削弱这些反应的宿主/肿瘤因素之间，很可能会存在一种“动态平衡”。因此，以疾病稳定和延长生存期形式出现的“患者反应”可能比严格遵循实体瘤疗效评价标准（RECIST）标准形式的“肿瘤反应”更适合作为监测指标。这可以表现为疫苗治疗后患者对后续治疗的获益增加。本文将回顾癌症疫苗所特有的这些现象，重点以前列腺癌疫苗作为疫苗治疗的范例。这种治疗方式的独特特征要求在设计癌症疫苗临床试验的方式以及评估患者获益的方式上都要考虑范式转变。
