Dendritic Cell Vaccine for Recurrent High-Grade Gliomas in Pediatric and Adult Subjects: Clinical Trial Protocol
Dendritic Cell Vaccine for Recurrent High-Grade Gliomas in Pediatric and Adult Subjects: Clinical Trial Protocol
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DOI：
10.1227/neu.0000000000000107
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发表时间：
2013-11-01
期刊：
影响因子：
4.8
通讯作者：
Goldberg, John
中科院分区：
文献类型：
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作者：
Shah, Ashish H.;Bregy, Amade;Goldberg, John
背景技术背景：尽管在了解多形性胶质母细胞瘤的基本发病机制方面取得了重大进展，但在过去25年中，患者的中位生存期变化不大。最近的研究表明，通过树突状细胞（DC）疫苗的免疫调节可能会刺激免疫系统对肿瘤抗原和潜在的增加生存。为了确定是否使用自体DC的辅助接种，（在加载来自自体难治性胶质瘤的肿瘤细胞裂解物后原位成熟）是安全的，可行的，对成人和儿童复发性高级别胶质瘤患者有益。方法：本研究设计为单中心、非随机、开放I期临床试验。将在术前入组总计20例恶性胶质瘤患者，为期2年。患者将给予佐剂疫苗接种与自体树突状细胞负载肿瘤裂解物后，最大的安全手术切除术。预期的结果：使用局部咪喹莫特接种疫苗前，预计在接种疫苗的患者的免疫应答和潜在的总生存率将大于在文献中所证明的。我们预计，将有最小的副作用（轻微皮炎）与此treatment.Discussion：在目前的试验中，我们评估免疫反应，安全性和生存使用一种新的疫苗协议在比利时开发，似乎显着增加某些科目的生存。然而，需要进行更大规模的随机临床研究，以充分评估这种疗法对复发和新诊断的胶质母细胞瘤的疗效。
BACKGROUND: Although there have been significant advances in understanding the basic pathogenesis of glioblastoma multiforme, the median survival of patients has changed little in the past 25 years. Recent studies have suggested that immune modulation through dendritic cell (DC) vaccines may stimulate the immune system against tumor antigens and potentially increase survival.OBJECTIVE: To determine whether the use of adjuvant vaccination with autologous DCs (matured in situ after being loaded with tumor cell lysate derived from autologous refractory gliomas) is safe, feasible, and beneficial for adult and pediatric patients with recurrent high-grade gliomas.METHODS: The study design is a single-center, nonrandomized, open phase I clinical trial. A total of 20 patients with malignant gliomas will be enrolled preoperatively over 2 years. Patients will be given adjuvant vaccination with autologous DCs loaded with tumor lysate after maximal safe surgical resection.EXPECTED OUTCOMES: Using topical imiquimod before vaccination, it is anticipated that the immune response in vaccinated patients and potentially Overall survival will be greater than that demonstrated in the literature. We anticipate that there will be minimal side effects (minor dermatitis) associated with this treatment.DISCUSSION: In the current trial, we assess immune response, safety, and survival using a novel vaccine protocol developed in Belgium that seems to markedly increase survival of certain subjects. Nevertheless, larger randomized clinical studies need to be performed to evaluate fully the efficacy of this therapy for both recurrent and newly diagnosed glioblastoma.