Advanced intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by limited response to standard therapeutic modalities, such as radiotherapy, chemotherapy, and targeted therapy. The prognosis for patients with advanced ICC is exceedingly bleak, with an overall survival of less than 1 year. In recent years, personalized neoantigen vaccines have emerged as a promising approach to augment the immune response against tumors. Clinical investigations are currently underway to evaluate the efficacy of neoantigen-based peptide, DNA, and dendritic cell vaccines. Herein, we present a noteworthy case of advanced ICC patients who experienced disease progression following relapse and subsequently received immunotherapy with a personalized neoantigen nanovaccine. This innovative treatment strategy involved the administration of a custom-designed neoantigen-based peptide nanovaccine tailored to the patient’s specific gene mutation profile subsequent to failure of first-line therapy. The clinical efficacy and anti-tumor immune responses were evaluated using various methods, including imaging, interferon-γ ELISPOT assay, and intracellular cytokine staining. Notably, the neoantigen nanovaccine elicited a robust and specific tumor-killing effect mediated by T cells, resulting in a durable response lasting up to 25 months. These findings highlight the potential of neoantigen-based immunotherapy as a novel therapeutic avenue for the management of advanced ICC.

晚期肝内胆管癌（ICC）是一种高度侵袭性的恶性肿瘤，其特征是对标准治疗方式（例如放疗、化疗和靶向治疗）反应有限。晚期ICC患者的预后极其黯淡，总生存期不到1年。近年来，个性化新抗原疫苗已成为增强肿瘤免疫反应的一种有前景的方法。目前正在进行临床研究，以评估基于新抗原的肽、DNA 和树突状细胞疫苗的功效。在此，我们介绍了一个值得注意的晚期 ICC 患者的病例，这些患者在复发后经历了疾病进展，随后接受了个性化新抗原纳米疫苗的免疫治疗。这种创新的治疗策略涉及在一线治疗失败后，根据患者的特定基因突变情况，施用定制设计的基于新抗原的肽纳米疫苗。使用多种方法评估临床疗效和抗肿瘤免疫反应，包括成像、干扰素-γ ELISPOT测定和细胞内细胞因子染色。值得注意的是，新抗原纳米疫苗引发了由 T 细胞介导的强大而特异性的肿瘤杀伤作用，从而产生持续长达 25 个月的持久反应。这些发现凸显了基于新抗原的免疫疗法作为治疗晚期 ICC 的新型治疗途径的潜力。