Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme
Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme
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DOI：
10.3171/jns/2008/108/5/0963
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发表时间：
2008-05-01
影响因子：
4.1
通讯作者：
Yosihmine, Toshiki
中科院分区：
文献类型：
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作者：
Izumoto, Shuichi;Tsuboi, Akihiro;Yosihmine, Toshiki
对象。本研究的目的是探讨WT1 （Wilms tumor 1）基因产物免疫治疗复发性多形性胶质母细胞瘤（GBM）患者的安全性和临床反应。21例WTI/HLA-A*2402阳性复发性GBM患者纳入了WT1疫苗治疗的11期临床研究。在所有患者中，肿瘤对标准治疗都有耐药性。患者每周皮内注射HLA-A*2402限制性修饰的9-mer WT1肽，持续12周。肿瘤大小，通过测量磁共振图像上的对比增强面积获得，每4周测定一次。在初次接种疫苗12周后，根据实体瘤应答评价标准（RECIST）对应答进行分析。达到所有有效反应的患者继续接种疫苗，直到肿瘤发生进展。评估初始WT1治疗后的无进展生存期和总生存期。该方案耐受性良好；仅在WT1疫苗注射部位出现局部红斑。临床反应：部分缓解2例，病情稳定10例，病情进展9例。没有病人有完全的反应。总有效率（完全或部分缓解）为9.5%，疾病控制率（完全或部分缓解及病情稳定）为57.1%。中位无进展生存期（PFS）为20.0周，6个月（26周）PFS率为33.3%。虽然是一项小型非随机对照试验，但该研究表明，WT1疫苗治疗WT1 /HLA-A*2402阳性复发性GBM患者是安全的，并产生了临床反应。基于这些结果，WT1疫苗治疗恶性胶质瘤患者的进一步临床研究是必要的。
Object. The object of this study was to investigate the safety and clinical responses of immunotherapy targeting the WT1 (Wilms tumor 1) gene product in patients with recurrent glioblastoma multiforme (GBM).Methods. Twenty-one patients with WTI/HLA-A*2402-positive recurrent GBM were included in a Phase 11 clinical study of WT1 vaccine therapy. In all patients, the tumors were resistant to standard therapy. Patients received intradermal injections of an HLA-A*2402-restricted, modified 9-mer WT1 peptide every week for 12 weeks. Tumor size, which was obtained by measuring the contrast-enhanced area on magnetic resonance images, was determined every 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST) 12 weeks after the initial vaccination. Patients who achieved ail effective response continued to be vaccinated until tumor progression occurred. Progression-free survival and overall survival after initial WT1 treatment were estimated.Results. The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The clinical responses were as follows: partial response in 2 patients, stable disease in 10 patients, and progressive disease in 9 patients. No patient had a complete response. The overall response rate (cases with complete or partial response) was 9.5%, and the disease control rate (cases with complete or partial response as well as those in which disease was stable) was 57.1%. The median progression-free survival (PFS) period was 20.0 weeks, and the 6-month (26-week) PFS rate was 33.3%.Conclusions. Although a small uncontrolled nonrandomized trial, this study showed that WT1 vaccine therapy for patients with WT1 /HLA-A*2402-positive recurrent GBM was safe and produced a clinical response. Based on these results, further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted.