Personalized vaccines directed to tumor mutations have recently gained significant momentum. On the basis of the concept of stimulating T-cell responses against neoantigens encoded by a tumor's host of personal mutations, these vaccines utilize genome or exome sequencing, mutation calling, and epitope prediction followed by manufacturing of a customized vaccine for each patient. In their 2012 Cancer Research publication, Castle and colleagues provided evidence that vaccinating with long peptide vaccines encompassing neoantigens can generate robust immune responses and induce antitumor activity in a mouse B16F10 melanoma. This approach, harnessing the exquisite specificity of mutations to the tumor and thus providing an effective target for cancer vaccines, was subsequently shown to be safe and immunogenic in a series of small first in man trials in patients with melanoma. The field has accelerated and expanded substantially over the last 5 years, propelled by increasing evidence for vaccine-mediated clinical efficacy, leading to ongoing registrational trials using personalized RNA neoantigen vaccines in patients with melanoma and several other malignancies. See related article by Castle and colleagues, Cancer Res 2012;72:1081–91

中文翻译：

---

针对肿瘤突变的个性化癌症疫苗：从小鼠到人类建立证据

针对肿瘤突变的个性化疫苗最近获得了巨大的发展势头。基于刺激 T 细胞针对肿瘤宿主个体突变编码的新抗原做出反应的概念，这些疫苗利用基因组或外显子组测序、突变识别和表位预测，然后为每位患者生产定制疫苗。 Castle 及其同事在其 2012 年《癌症研究》出版物中提供了证据，表明接种包含新抗原的长肽疫苗可以在小鼠 B16F10 黑色素瘤中产生强大的免疫反应并诱导抗肿瘤活性。这种方法利用了肿瘤突变的精确特异性，从而为癌症疫苗提供了有效的靶标，随后在一系列针对黑色素瘤患者的小型首次人体试验中证明了其安全性和免疫原性。在越来越多的疫苗介导的临床功效证据的推动下，该领域在过去 5 年里加速发展并大幅扩展，导致在黑色素瘤和其他几种恶性肿瘤患者中使用个性化 RNA 新抗原疫苗正在进行注册试验。参见 Castle 及其同事的相关文章，Cancer Res 2012；72:1081–91