文章：

预防肿瘤的疫苗

Vaccines for tumour prevention

原文发布日期：2006-03-01

DOI: 10.1038/nrc1815

类型: Review Article

开放获取: 否

要点：

1. Numerous tumour-challenge experiments in immunized rodents and studies with cancer-prone genetically modified mice show that vaccines can prevent tumour onset and progression.
2. Effective prevention requires vaccination at an early stage of tumour formation. The ability of a vaccine to protect decreases when a precancerous lesion reaches a more advanced stage.
3. The main reason why vaccines are effective in tumour prevention is that the target is a small precancerous lesion. So, most of the difficulties that are encountered by vaccines in the therapy of established tumours do not apply to prevention.
4. The immune mechanisms leading to the blocking of carcinogenesis are not solely dependent on cytotoxic T cells — they mostly rest on the coordinated activation of multiple mechanisms. CD4⁺ T-helper cells, the release of interferon-γ and the production of antibodies are often the key features of a sustained prevention.
5. The extended time-frame that characterizes tumour prevention favours the immune selection of escaping tumour-cell clones that have lost expression of target antigens. When the vaccine-elicited immune response is directed against antigens that control the neoplastic process (oncoantigens), the likelihood of this kind of selection is markedly reduced.
6. Oncoantigens expressed on tumour cell membranes are accessible to antibody-mediated reactions. These reactions are not impaired by down-modulation of major histocompatability complex class I (MHC-I) glycoproteins on the surface of tumour cells, which is a frequent mechanism by which tumours escape immune surveillance.
7. Because oncoantigens are self-antigens, there is the risk of vaccine-elicited autoimmune reactions. Overexpression of oncoantigens by the tumour and elicitation of low-avidity reactions in tolerant hosts render the immune reaction selective and reduce this risk.
8. Preclinical results in transgenic mice provide a rationale for the use of vaccines in the prevention of human tumours in high-risk individuals with multifocal pre-neoplastic lesions, a genetic predisposition to cancer or following carcinogenic exposures. Translation of these results to the clinical setting requires sequential approaches, starting from the prevention of tumour relapse in cancer patients after successful conventional management.

要点翻译：

1. 在免疫接种的啮齿类动物中进行的多次肿瘤攻击实验以及对易患癌症的转基因小鼠的研究表明，疫苗能够预防肿瘤的发生和进展。
2. 有效的预防需要在肿瘤形成的早期阶段进行疫苗接种。当前癌病变发展到更晚期阶段时，疫苗的保护能力会下降。
3. 疫苗能有效预防肿瘤的主要原因在于其靶目标是小型癌前病变。因此，疫苗在治疗已形成肿瘤时遇到的大多数困难在预防中并不存在。
4. 导致癌变阻断的免疫机制并不 solely 依赖于细胞毒性T细胞——它们主要依赖于多种机制的协同激活。CD4+辅助性T细胞、γ干扰素的释放和抗体的产生通常是持续预防的关键特征。
5. 肿瘤预防所具有的延长时间框架有利于逃逸性肿瘤细胞克隆（即失去靶抗原表达的克隆）的免疫选择。当疫苗引发的免疫反应针对控制肿瘤过程的抗原（肿瘤抗原）时，这类选择的可能性会显著降低。
6. 肿瘤细胞膜上表达的肿瘤抗原可被抗体介导的反应所识别。这些反应不会因肿瘤细胞表面主要组织相容性复合体I类（MHC-I）糖蛋白的下调而受损，而后者是肿瘤逃避免疫监视的常见机制。
7. 由于肿瘤抗原是自身抗原，存在疫苗引发自身免疫反应的风险。肿瘤对肿瘤抗原的过度表达以及在耐受宿主中引发低亲和力反应，使得免疫反应具有选择性，从而降低了这种风险。
8. 在转基因小鼠中获得的临床前结果，为在高风险人群（患有多灶性癌前病变、具有癌症遗传易感性或接触致癌物后）中使用疫苗预防人类肿瘤提供了理论依据。将这些结果转化为临床应用需要采用序贯方法，从预防癌症患者经成功常规治疗后的肿瘤复发开始。

英文摘要：

Despite tremendous progress in basic and epidemiological research, effective prevention of most types of cancer is still lacking. Vaccine use in cancer therapy remains a promising but difficult prospect. However, new mouse models that recapitulate significant features of human cancer progression show that vaccines can keep precancerous lesions under control and might eventually be the spearhead of effective and reliable ways to prevent cancer.

摘要翻译： 

尽管基础和流行病学研究取得了巨大进展，但大多数类型癌症的有效预防手段仍然缺乏。疫苗在癌症治疗中的应用仍是一个充满希望但困难重重的方向。然而，新的小鼠模型重现了人类癌症进展的关键特征，显示疫苗可以控制癌前病变，并可能成为有效且可靠预防癌症的先锋手段。

原文链接：

Vaccines for tumour prevention