Targeting the Heterogeneity of Cancer with Individualized Neoepitope Vaccines
Targeting the Heterogeneity of Cancer with Individualized Neoepitope Vaccines
复制标题
DOI：
10.1158/1078-0432.ccr-15-1509
复制
发表时间：
2016-04-15
影响因子：
11.5
通讯作者：
Sahin, Ugur
中科院分区：
文献类型：
--
作者：
Tuereci, Oezlem;Vormehr, Mathias;Sahin, Ugur
与患者的MHC结合并被自体T细胞识别的体细胞突变（新表位）是理想的癌症疫苗靶标。由于在健康组织中缺乏表达，它们联合收割机有利的安全性特征和免疫原性的高可能性，因为识别新表位的T细胞不受中枢免疫耐受的影响。多年来，人们一直在探索癌症中突变的蛋白质（新抗原）作为疫苗靶点。然而，共享（“公共”）突变是罕见的，因为给定肿瘤中的绝大多数癌症突变对于个体患者是独特的。最近，出现了真正个性化的癌症疫苗接种的新概念，它利用了患者特异性“私人”突变的巨大来源。科学进步和技术突破的同时实现了“突变组“的快速、成本效益高和全面的作图，”突变组“是个体肿瘤中的体细胞突变的整体，以及新表位的合理选择。如何将肿瘤突变组数据转化为可操作的知识，以“按需”定制个性化疫苗，已成为一个具有范式转变潜力的新研究领域。本文综述了这类疫苗的临床开发。(C)2016年AACR。
Somatic mutations binding to the patient's MHC and recognized by autologous T cells (neoepitopes) are ideal cancer vaccine targets. They combine a favorable safety profile due to a lack of expression in healthy tissues with a high likelihood of immunogenicity, as T cells recognizing neoepitopes are not shaped by central immune tolerance. Proteins mutated in cancer (neoantigens) shared by patients have been explored as vaccine targets for many years. Shared ("public") mutations, however, are rare, as the vast majority of cancer mutations in a given tumor are unique for the individual patient. Recently, the novel concept of truly individualized cancer vaccination emerged, which exploits the vast source of patient-specific "private" mutations. Concurrence of scientific advances and technological breakthroughs enables the rapid, cost-efficient, and comprehensive mapping of the "mutanome, "which is the entirety of somatic mutations in an individual tumor, and the rational selection of neoepitopes. How to transform tumor mutanome data to actionable knowledge for tailoring individualized vaccines "on demand" has become a novel research field with paradigm-shifting potential. This review gives an overview with particular focus on the clinical development of such vaccines. (C) 2016 AACR.