Dalgleish A G, Whelan M A
Department of Oncology, St. George's Hospital Medical School, Cranmer Terrace, SW17 0RE, London, UK.
Cancer Immunol Immunother. 2006 Aug;55(8):1025-32. doi: 10.1007/s00262-006-0128-8. Epub 2006 Feb 28.
The development of cancer vaccines has been one of the several false dawns in which initial promising Phase I and Phase II clinical data have not been followed up with conclusive Phase III trials. In this review, we describe some of the successes and failures, and review the most likely reasons for Phase III failure, such as protocol changes, which are common between Phase II and III, and poorly defined patient groups. Nevertheless, significant survival results have been reported with autologous vaccines for colorectal, renal and, more recently, prostate cancer. In addition, it is becoming evident that immunotherapy is potentially synergistic with other treatment modalities, such as chemotherapy, which can reduce T-regulatory activity that inhibits the immune response to cancer vaccines. This potential for synergy should allow cancer vaccines to become part of the standard treatment regimen for many common tumours.
癌症疫苗的研发历程中曾出现过多次类似虚假曙光的情况,即最初在I期和II期临床试验中呈现出有希望的数据,但后续却未能通过具有决定性意义的III期试验。在本综述中,我们阐述了一些成功与失败的案例,并审视了III期试验失败的最可能原因,比如方案变更(这在II期和III期试验中较为常见)以及患者群体定义不明确等问题。尽管如此,已有报道称自体疫苗在治疗结直肠癌、肾癌以及最近的前列腺癌方面取得了显著的生存效果。此外,越来越明显的是,免疫疗法与其他治疗方式(如化疗)可能具有协同作用,化疗可以降低抑制对癌症疫苗免疫反应的调节性T细胞活性。这种协同潜力应能使癌症疫苗成为许多常见肿瘤标准治疗方案的一部分。