Department of Pathology, Sapporo Medical University, Sapporo, Japan.
Joint Research Center for Immunoproteogenomics, Sapporo Medical University, Sapporo, Japan.
Sci Adv. 2024 Sep 20;10(38):eado6491. doi: 10.1126/sciadv.ado6491. Epub 2024 Sep 18.
Neoantigens arising from somatic mutations are tumor specific and induce antitumor host T cell responses. However, their sequences are individual specific and need to be identified for each patient for therapeutic applications. Here, we present a proteogenomic approach for neoantigen identification, named Neoantigen Selection using a Surrogate Immunopeptidome (NESSIE). This approach uses an autologous wild-type immunopeptidome as a surrogate for the tumor immunopeptidome and allows human leukocyte antigen (HLA)-agnostic identification of both HLA class I (HLA-I) and HLA class II (HLA-II) neoantigens. We demonstrate the direct identification of highly immunogenic HLA-I and HLA-II neoantigens using NESSIE in patients with colorectal cancer and endometrial cancer. Fresh or frozen tumor samples are not required for analysis, making it applicable to many patients in clinical settings. We also demonstrate tumor prevention by vaccination with selected neoantigens in a preclinical mouse model. This approach may benefit personalized T cell-mediated immunotherapies.
源自体细胞突变的新生抗原具有肿瘤特异性，并能诱导抗肿瘤宿主 T 细胞反应。然而，它们的序列是个体特异性的，需要为每个患者进行鉴定，才能用于治疗应用。在这里，我们提出了一种用于新生抗原鉴定的蛋白质基因组学方法，名为使用替代免疫肽组学进行新生抗原选择 (NESSIE)。该方法使用自体野生型免疫肽组作为肿瘤免疫肽组的替代物，允许对 HLA 类 I (HLA-I) 和 HLA 类 II (HLA-II) 新生抗原进行 HLA 无偏见鉴定。我们证明了 NESSIE 可直接鉴定结直肠癌和子宫内膜癌患者中具有高度免疫原性的 HLA-I 和 HLA-II 新生抗原。分析不需要新鲜或冷冻的肿瘤样本，使其适用于临床环境中的许多患者。我们还在临床前小鼠模型中证明了用选定的新生抗原进行疫苗接种可预防肿瘤。这种方法可能有益于个性化的 T 细胞介导的免疫疗法。
