Department of Immunology, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
Cancer Immunol Immunother. 2013 May;62(5):967-74. doi: 10.1007/s00262-013-1422-x. Epub 2013 Apr 19.
The idea that individual tumors are antigenically unique has been around since the very dawn of our recognition of adaptive immune response to tumors. That idea has inspired a small number of attempts at individualized immunotherapy of human cancers. Such previous attempts for solid tumors have been hobbled by an inability to define the individually unique antigenic repertoire of tumors because of technological difficulties. The new availability of rapid and cheap high throughput DNA sequencing promises to overcome that hurdle. Using this new ability, coupled with bio-informatic tools, it is now possible to define the immunogenic repertoire of any tumor to a high degree of granularity within a practical time frame and an acceptable cost. The development of these ideas, and a small number of such studies that underscore this promise, is discussed. This new way--of characterizing the tumor immunome through characterization of the tumor genome--has distinct challenges, including selection of the appropriate peptides, choosing methods of immunizations that can incorporate tens of epitopes, and addressing issues of antigenic heterogeneity of tumors. However, tools for meeting these challenges exist and are emergent.
自我们认识到适应性免疫反应对肿瘤的作用以来,个体肿瘤具有独特的抗原性这一观点就一直存在。这一观点激发了对人类癌症进行个体化免疫治疗的少量尝试。由于技术困难,以前针对实体瘤的此类尝试受到阻碍,无法确定肿瘤独特的抗原谱。快速廉价的高通量 DNA 测序的新出现有望克服这一障碍。利用这种新能力,结合生物信息学工具,现在可以在实际时间框架和可接受的成本内,以高度的粒度来定义任何肿瘤的免疫原性谱。本文讨论了这些想法的发展,以及少数强调这一承诺的此类研究。这种通过肿瘤基因组特征来描述肿瘤免疫组的新方法具有明显的挑战,包括选择适当的肽,选择可以包含数十个表位的免疫接种方法,以及解决肿瘤抗原异质性的问题。然而,用于应对这些挑战的工具已经存在并且正在出现。