Background/Objectives: Neoantigens have attracted attention as ideal therapeutic targets for anti-tumour immunotherapy because the T cells that respond to neoantigens are not affected by central immune tolerance. Recent findings have revealed that the activation of CD4-positive T cells plays a central role in antitumor immunity, and thus targeting human leukocyte antigen (HLA) class II-restricted neoantigens, which are targets of CD4-positive T cells, is of significance. However, there are very few detailed reports of neoantigen vaccine therapies that use an HLA class II-restricted long peptide. In the present study, we retrospectively analysed the ability of HLA class II-restricted neoantigen-pulsed dendritic cell vaccines to induce immune response in five breast cancer patients.Methods: We performed whole exome and RNA sequencing of breast cancer tissues and neoantigen prediction using an in silico pipeline. We then administered dendritic cells pulsed with synthesized an HLA class II-restricted long peptide containing an epitope with high affinity to HLA class I in the lymph node.Results: ELISPOT analysis confirmed that a T-cell response specific for the HLA class II-restricted neoantigen was induced in all cases. TCR repertoire analysis of peripheral blood mononuclear cells before and after treatment in three patients showed increases of specific T-cell clones in two of the three patients. Importantly, no recurrence was observed in all patients.Conclusions:Our analysis demonstrated the immunological efficacy of the HLA class II-restricted neoantigen peptide dendritic cell vaccine against breast cancer and provides useful information for the development of neoantigen vaccine therapy for breast cancer.
背景/目的：新抗原因其能诱导不受中枢免疫耐受影响的T细胞应答，已成为肿瘤免疫治疗的理想靶点。近期研究表明，CD4阳性T细胞的激活在抗肿瘤免疫中发挥核心作用，因此靶向CD4阳性T细胞所识别的人类白细胞抗原（HLA）II类限制性新抗原具有重要意义。然而，目前关于采用HLA II类限制性长肽的新抗原疫苗疗法的详细报道极为有限。本研究回顾性分析了HLA II类限制性新抗原负载树突状细胞疫苗在五例乳腺癌患者中诱导免疫应答的能力。 方法：我们对乳腺癌组织进行全外显子组测序和RNA测序，并通过生物信息学流程预测新抗原。随后在淋巴结区域注射负载合成肽的树突状细胞疫苗，该合成肽为包含HLA I类高亲和力表位的HLA II类限制性长肽。 结果：ELISPOT分析证实所有病例均诱导出针对HLA II类限制性新抗原的特异性T细胞应答。对其中三例患者治疗前后外周血单个核细胞的T细胞受体谱分析显示，两例患者体内特异性T细胞克隆有所增加。值得注意的是，所有患者均未出现复发。 结论：本研究证实了HLA II类限制性新抗原肽树突状细胞疫苗在乳腺癌治疗中的免疫学效力，为开发乳腺癌新抗原疫苗疗法提供了重要参考依据。
肿瘤(癌症)患者之家