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针对复发性高级别胶质瘤和髓母细胞瘤患儿及年轻成人患者的巨细胞病毒抗原pp65多肽疫苗：一期临床试验

A peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma: a phase 1 trial原文发布日期: 2025-06-12英文摘要:

摘要翻译：

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文章 :

针对复发性高级别胶质瘤和髓母细胞瘤患儿及年轻成人患者的巨细胞病毒抗原pp65多肽疫苗：一期临床试验

A peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma: a phase 1 trial

原文发布日期: 2025-06-12

英文摘要:

The human cytomegalovirus (CMV) antigen pp65 is expressed in high-grade glioma (HGG) and medulloblastoma but not in the adjacent brain. This single-arm phase 1 trial (NCT03299309) assessed the safety and immunogenicity of a peptide vaccine (PEP-CMV) targeting pp65 in individuals (3–35 years old) with recurrent HGG or medulloblastoma. Thirty-six individuals with HGG received PEP-CMV. The mean age was 22.75 ± 9.34 years. The primary outcome, percentage of unacceptable toxicity, was met. The maximum-grade adverse events (AE) related to PEP-CMV were 17 grade 1 AEs, 15 grade 2 AEs, 1 grade 3 AE (pyramidal tract syndrome) and 1 grade 4 AE (cerebral edema). As a secondary outcome, in 21 individuals with evaluable data, T cell reactivity, measured as change in baseline interferon-γ pp65 enzyme-linked immunospot assay reactivity, had an estimated increase of 46 spots (95% confidence interval (95% CI): 8, 194) after treatment with PEP-CMV. As exploratory endpoints, the median progression-free survival was 2.5 months (95% CI: 2.2, 3.2), and median overall survival was 6.5 months (95% CI: 4.6, 8.4). PEP-CMV is well tolerated and elicits an antigen-specific immune response in individuals with multiply recurrent HGG. Only two individuals with medulloblastoma were enrolled, showing one grade 3 encephalopathy possibly related to PEP-CMV, while neither had postvaccine immune assessments due to progression-free survival and overall survival less than 2 months.

摘要翻译：

人类巨细胞病毒（CMV）抗原pp65在高级别胶质瘤（HGG）和髓母细胞瘤中表达，但在邻近脑组织中不表达。这项单臂1期临床试验（NCT03299309）评估了靶向pp65的多肽疫苗（PEP-CMV）在复发型HGG或髓母细胞瘤患者（3-35岁）中的安全性和免疫原性。36例HGG患者接受了PEP-CMV治疗，平均年龄为22.75±9.34岁。主要终点——不可接受毒性发生率达标。与PEP-CMV相关的最高级别不良事件（AE）包括：17例1级AE、15例2级AE、1例3级AE（锥体束综合征）及1例4级AE（脑水肿）。作为次要终点，在21例可评估数据患者中，通过干扰素-γ pp65酶联免疫斑点试验检测的T细胞反应性显示，PEP-CMV治疗后基线反应性平均增加46个斑点（95%置信区间[95%CI]：8,194）。探索性终点显示：中位无进展生存期为2.5个月（95%CI：2.2,3.2），中位总生存期为6.5个月（95%CI：4.6,8.4）。PEP-CMV在多次复发的HGG患者中耐受性良好，并能引发抗原特异性免疫反应。仅纳入的2例髓母细胞瘤患者中，1例出现可能与PEP-CMV相关的3级脑病，由于无进展生存期和总生存期均不足2个月，两者均未进行疫苗接种后免疫评估。