文章：

用于疫苗开发的肿瘤相关t细胞表位的鉴定

Identification of tumour-associated t-cell epitopes for vaccine development

原文发布日期：2002-07-01

DOI: 10.1038/nrc841

类型: Review Article

开放获取: 否

要点：

1. T-cell epitopes from tumour antigens have been included in many vaccination studies, and their potential to induce antitumour immune responses has become manifest. Nevertheless, the clinical outcome of such studies has to be improved.
2. The number of known epitopes is still limited; therefore, some tumours cannot be treated by immunotherapeutic approaches. For others, the efficacy is not yet optimal.
3. T-cell epitopes from tumour antigens can be defined by two principal strategies: one starts from an existing T-cell response and identifies the target of the response, whereas the other uses the sequence of a tumour antigen and employs epitope prediction to identify the relevant epitopes.
4. New tumour antigens can be discovered by analysing the specificity of existing T-cell responses, or by screening strategies such as the SEREX programme, comparative proteome analysis or gene-expression profiling.
5. To improve the clinical outcome of antitumour vaccinations, tumour-escape mechanisms have to be avoided by the use of efficient, multitarget vaccines.
6. With the growing number of T-cell epitopes, it will become feasible to design patient-specific, individual vaccines that address several different antigens from one tumour and several HLA specificities, including class-II-restricted epitopes.

要点翻译：

1. 肿瘤抗原中的T细胞表位已被纳入众多疫苗研究，其诱导抗肿瘤免疫反应的潜力已得到明确验证。然而，此类研究的临床疗效仍需提升。
2. 已知表位数量仍然有限，因此部分肿瘤无法通过免疫治疗方法得到治疗。对其他肿瘤而言，现有疗法的有效性尚未达到最优。
3. 肿瘤抗原T细胞表位可通过两种主要策略进行鉴定：一种从现有T细胞反应出发，通过识别反应靶标确定表位；另一种则利用肿瘤抗原序列，通过表位预测技术筛选相关表位。
4. 新肿瘤抗原的发现可通过分析现有T细胞反应的特异性，或采用SEREX技术、比较蛋白质组分析及基因表达谱分析等筛选策略实现。
5. 为提升抗肿瘤疫苗的临床效果，需采用高效的多靶点疫苗来规避肿瘤逃逸机制。
6. 随着T细胞表位数量的持续增长，设计针对个体患者的定制化疫苗将成为可能——这种疫苗可同时靶向同一肿瘤的多种不同抗原，并覆盖多种HLA特异性（包括II类限制性表位）。

英文摘要：

Ten years ago, the first melanoma patient was successfully treated by vaccination with a short peptide, which was, in fact, the first tumour-specific T-cell epitope ever defined — MAGE. Since then, a number of clinical vaccination studies have underlined the potential of tumour-specific T-cell epitopes. But, how can we identify more epitopes to improve their efficacy as an anticancer treatment?

摘要翻译： 

十年前，第一例黑色素瘤患者通过接种短肽疫苗成功获得治疗，该短肽实际上是首个被定义的肿瘤特异性T细胞表位——MAGE。自此，多项临床疫苗研究强调了肿瘤特异性T细胞表位的潜力。但我们如何才能鉴定出更多表位，以提高其作为抗癌治疗的疗效？

原文链接：

Identification of tumour-associated t-cell epitopes for vaccine development