Immunotherapy with neoantigens presented by major histocompatibility complex (MHC) is one of the most promising approaches in cancer treatment. Using this approach, cancer vaccines can be designed to target tumor‐specific mutations that are not found in normal tissues. Clinical trials have demonstrated an increased immune response and eradication of tumors after injecting synthetic peptides selected from the immunopeptidome. Although the sequence of MHC binding peptides can be predicted from genome sequencing and prediction algorithms, this approach results in large numbers of predicted peptides, requiring the confirmation by mass spectrometry (MS) analysis. Identification of MHC peptides by direct MS analysis of immunopeptidome is accurate and sensitive, with tens of thousands of unique peptides potentially identified from either cancer cell line or tumor tissue. Peptides with mutations can also be identified with patient‐specific protein databases constructed from genome or transcriptome sequencing data. MS analysis also enables the characterization of the post‐translational modifications (PTMs) of those antigens that cannot be predicted. Moreover, PTMs were found to be more efficient in triggering an immune response. In addition to reviewing recent advances in the identification of neoantigens using MS, the techniques for cancer vaccine candidate selection and formulation, vaccine delivery systems, and the potential for use in combination with other therapeutics are also discussed. It is anticipated that MS‐based techniques will play an important role in future cancer vaccine development. © 2019 John Wiley & Sons Ltd. Mass Spec Rev 40:110–125, 2021.

中文翻译：

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使用质谱法鉴定 MHC 肽用于新抗原发现和癌症疫苗开发

主要组织相容性复合体（MHC）呈递的新抗原的免疫治疗是癌症治疗中最有前途的方法之一。使用这种方法，可以设计癌症疫苗以针对正常组织中未发现的肿瘤特异性突变。临床试验表明，注射选自免疫肽组的合成肽后，免疫反应增强，肿瘤根除。尽管可以通过基因组测序和预测算法预测 MHC 结合肽的序列，但这种方法会导致大量预测肽，需要通过质谱 (MS) 分析进行确认。通过免疫肽组的直接 MS 分析鉴定 MHC 肽准确且灵敏，数以万计的独特肽可能从癌细胞系或肿瘤组织中鉴定出来。还可以使用由基因组或转录组测序数据构建的患者特异性蛋白质数据库来鉴定具有突变的肽。MS 分析还能够表征那些无法预测的抗原的翻译后修饰 (PTM)。此外，发现 PTM 在触发免疫反应方面更有效。除了回顾使用 MS 识别新抗原的最新进展外，还讨论了癌症候选疫苗选择和配制、疫苗递送系统以及与其他疗法联合使用的潜力。预计基于 MS 的技术将在未来的癌症疫苗开发中发挥重要作用。