文章：

合成长肽疫苗对恶性疾病的免疫治疗

Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines

原文发布日期：2008-05-01

DOI: 10.1038/nrc2373

类型: Review Article

开放获取: 否

要点：

1. Many attempts at cancer immunotherapy have been conducted; however, apart from melanoma, in which impressive clinical responses have been noted in a small minority of patients, the overall results have been disappointing.
2. Therapeutic vaccines require induction of robust cell-mediated immunity, capable of attacking and eliminating abnormal antigen-bearing cells. This calls for close collaboration between cells of the innate and adaptive immune systems.
3. A popular approach to therapeutic cancer vaccination has been vaccination with exact major histocompatibility complex (MHC)-binding peptides derived from the sequence of tumour-associated antigens. However, this approach is far from optimal because it can lead to immunological tolerance of the immunizing antigens.
4. Peptide vaccines have been improved by the inclusion of agonists of the Toll-like receptors, the expression of epitopes to induce by cytotoxic T cells (Tc) and T helper cells within the same peptide and an increase in the length of the peptide used.
5. Synthetic long peptide (SLP) vaccines have evolved as a simple solution for the many problems that have surfaced with minimal Tc peptide vaccines. SLP are not able to bind directly to MHC class I and their presentation to Tc therefore indicates that they have to be taken up and processed before they are presented. As a result SLP can induce a more effective immune response.
6. SLP have recently entered phase I/II clinical trials in patients with premalignant and malignant human papillomavirus-induced cancers with promising results.

要点翻译：

1. 已进行过许多癌症免疫疗法的尝试；然而，除黑色素瘤（在少数患者中观察到显著的临床反应）外，总体结果令人失望。
2. 治疗性疫苗需要诱导强大的细胞介导免疫，能够攻击并清除携带异常抗原的细胞。这要求先天性与适应性免疫系统的细胞间密切协作。
3. 癌症治疗性疫苗的主流方法是通过源自肿瘤相关抗原序列的精确主要组织相容性复合体（MHC）结合肽进行接种。但这种方法远非最优选择，因为它可能导致对免疫抗原的免疫耐受。
4. 通过引入Toll样受体激动剂、在同一肽段内表达细胞毒性T细胞（Tc）和辅助性T细胞诱导表位，以及增加所用肽段长度，肽疫苗已得到改进。
5. 合成长肽（SLP）疫苗已成为解决最小Tc肽疫苗所浮现诸多问题的简易方案。SLP不能直接与MHC I类分子结合，因此它们被呈递给Tc细胞的前提是需要经过摄取和处理过程。这使得SLP能诱导更有效的免疫反应。
6. 近期SLP已进入针对人乳头瘤病毒引起的癌前病变和恶性肿瘤患者的I/II期临床试验，并取得了可喜的成果。

英文摘要：

This Review deals with recent progress in the immunotherapy of established (pre)malignant disease of viral or non-viral origin by synthetic vaccines capable of inducing robust T-cell responses. The most attractive vaccine compounds are synthetic long peptides (SLP) corresponding to the sequence of tumour viral antigens or tumour-associated non-viral antigens. Crucial to induction of therapeutic T-cell immunity is the capacity of SLP to deliver specific cargo to professional antigen-presenting cells (dendritic cells (DC)). Proper DC activation then induces the therapeutic CD4+ and CD8+ T-cell responses that are associated with regression of established (pre)malignant lesions, including those induced by high-risk human papilloma virus.

摘要翻译： 

本综述介绍了通过能够诱导强效T细胞应答的合成疫苗，对病毒或非病毒来源的已建立（癌前）恶性疾病进行免疫治疗的最新进展。最具吸引力的疫苗组分为对应于肿瘤病毒抗原序列或肿瘤相关非病毒抗原序列的合成长肽（SLP）。诱导治疗性T细胞免疫的关键在于SLP将特定“货物”递送至专职抗原提呈细胞（树突状细胞，DC）的能力。恰当的DC激活随后可诱导治疗性CD4+和CD8+ T细胞应答，这些应答与已建立（癌前）恶性病变的消退相关，包括由高危型人乳头瘤病毒诱导的病变。

原文链接：

Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines