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试验观察:癌症治疗中的肽疫苗。

Trial watch: Peptide vaccines in cancer therapy.

机构信息

Institut Gustave Roussy; Villejuif, France ; Université Paris-Sud/Paris XI; Le Kremlin-Bicêtre, France ; INSERM, U848; Villejuif, France.

出版信息

Oncoimmunology. 2012 Dec 1;1(9):1557-1576. doi: 10.4161/onci.22428.

Abstract

Prophylactic vaccination constitutes one of the most prominent medical achievements of history. This concept was first demonstrated by the pioneer work of Edward Jenner, dating back to the late 1790s, after which an array of preparations that confer life-long protective immunity against several infectious agents has been developed. The ensuing implementation of nation-wide vaccination programs has de facto abated the incidence of dreadful diseases including rabies, typhoid, cholera and many others. Among all, the most impressive result of vaccination campaigns is surely represented by the eradication of natural smallpox infection, which was definitively certified by the WHO in 1980. The idea of employing vaccines as anticancer interventions was first theorized in the 1890s by Paul Ehrlich and William Coley. However, it soon became clear that while vaccination could be efficiently employed as a preventive measure against infectious agents, anticancer vaccines would have to (1) operate as therapeutic, rather than preventive, interventions (at least in the vast majority of settings), and (2) circumvent the fact that tumor cells often fail to elicit immune responses. During the past 30 y, along with the recognition that the immune system is not irresponsive to tumors (as it was initially thought) and that malignant cells express tumor-associated antigens whereby they can be discriminated from normal cells, considerable efforts have been dedicated to the development of anticancer vaccines. Some of these approaches, encompassing cell-based, DNA-based and purified component-based preparations, have already been shown to exert conspicuous anticancer effects in cohorts of patients affected by both hematological and solid malignancies. In this Trial Watch, we will summarize the results of recent clinical trials that have evaluated/are evaluating purified peptides or full-length proteins as therapeutic interventions against cancer.

摘要

预防接种是医学史上最杰出的成就之一。这一概念最早由爱德华·詹纳(Edward Jenner)于 1790 年代后期的开创性工作提出,此后开发了一系列制剂,可以提供针对多种感染原的终身保护性免疫。随后实施的全国性疫苗接种计划实际上减少了包括狂犬病、伤寒、霍乱和许多其他疾病的发病率。在所有这些成就中,疫苗接种运动最令人印象深刻的结果无疑是消灭了天花感染,世界卫生组织于 1980 年正式宣布这一结果。将疫苗作为抗癌干预措施的想法最早是在 19 世纪 90 年代由保罗·埃尔利希(Paul Ehrlich)和威廉·科利(William Coley)提出的。然而,很快就清楚了,虽然疫苗接种可以作为针对感染原的有效预防措施,但抗癌疫苗必须(1)作为治疗性干预措施,而不是预防性干预措施(至少在绝大多数情况下如此),并且(2)规避肿瘤细胞通常无法引发免疫反应的事实。在过去的 30 年中,随着人们认识到免疫系统并非对肿瘤无反应(如最初认为的那样),以及恶性细胞表达肿瘤相关抗原,因此可以将其与正常细胞区分开来,人们为开发抗癌疫苗付出了巨大努力。其中一些方法包括基于细胞的、基于 DNA 的和基于纯化成分的制剂,已经在受血液系统恶性肿瘤和实体恶性肿瘤影响的患者群体中显示出显著的抗癌作用。在本试验观察中,我们将总结最近评估/正在评估作为治疗干预癌症的纯化肽或全长蛋白的临床试验结果。

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