Faktor Jakub, Hernychová Lenka, Vojtěšek Bořivoj, Hupp Theodore
Klin Onkol. 2018 Winter;31(Suppl 2):102-107. doi: 10.14735/amko20182S102.
Although immune responses to “cancer neoantigens” have been known for decades, the first neoantigen vaccines emerged only very recently. Current developments in genomics and proteomics have enabled descriptions of tumor mutational landscapes, and the immunogenicity of corresponding neoantigens can now be predicted either in silico or in vitro. Cancer regression could be achieved via a combination of neoantigen vaccination and an appropriate immunology approach. Research in model organisms and the results of initial clinical trials of neoantigen vaccines have shown them to be effective.
We aim to emphasize the importance of neoantigen vaccines in personalized cancer treatment and describe their preparation. We summarize mutations leading to expression of an immunogenic antigen necessary for vaccine development. The processes leading to activation of T-cell anticancer immunity in a patient are briefly introduced. We especially focus on the identification of high confidence neoantigens by next-generation sequencing (NGS) and mass spectrometry (MS), which is key element in the process of designing neoantigen vaccines. Briefly, we describe a proteogenomic platform for confident identification of mutant peptides in biological material. We mention the possibility of neoantigen quantification in biological material using mass spectrometry such as SRM (selected reaction monitoring) and SWATH (sequential windowed acquisition of all theoretical fragment ion spectra). Successful clinical studies demonstrating the potential of neoantigen vaccination in personalized cancer treatment are summarized at the end of the paper. Key words: vaccination - mass spectrometry - neoplasms - organ-specific neoantigen This work was supported by the project MEYS - NPS I - LO1413. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 9. 7. 2018.
尽管对“癌症新抗原”的免疫反应已为人所知数十年，但首批新抗原疫苗直到最近才出现。基因组学和蛋白质组学的当前发展使得能够描述肿瘤突变图谱，并且现在可以在计算机上或体外预测相应新抗原的免疫原性。通过新抗原疫苗接种和适当的免疫学方法相结合可以实现癌症消退。对模式生物的研究以及新抗原疫苗的初步临床试验结果表明它们是有效的。
我们旨在强调新抗原疫苗在个性化癌症治疗中的重要性并描述其制备方法。我们总结了导致疫苗开发所需的免疫原性抗原表达的突变。简要介绍了患者体内T细胞抗癌免疫激活的过程。我们特别关注通过下一代测序（NGS）和质谱（MS）鉴定高可信度新抗原，这是设计新抗原疫苗过程中的关键要素。简要地说，我们描述了一个用于可靠鉴定生物材料中突变肽的蛋白质基因组学平台。我们提到了使用质谱（如选择反应监测（SRM）和全理论碎片离子光谱的顺序窗口采集（SWATH））对生物材料中的新抗原进行定量的可能性。本文末尾总结了成功的临床研究，这些研究证明了新抗原疫苗接种在个性化癌症治疗中的潜力。关键词：疫苗接种 - 质谱 - 肿瘤 - 器官特异性新抗原 本研究得到了MEYS - NPS I - LO1413项目的支持。作者声明他们在研究中使用的药物、产品或服务方面没有潜在的利益冲突。编辑委员会声明该手稿符合ICMJE对生物医学论文的建议。接受日期：2018年7月9日。
