肿瘤细胞治疗研究
英文原题：Adjuvant Wilms' tumour 1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high-grade glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase I/II clinical trial in Belgium.
Adjuvant Wilms' tumour 1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high-grade glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase I/II clinical trial in Belgium.
弥漫性内生性脑桥胶质瘤（DIPG）和儿童高级别胶质瘤（pHGG）是侵袭性胶质肿瘤，常规治疗手段效果不佳。基于树突状细胞（DC）的免疫治疗正被研究作为一种有前景且安全的辅助疗法。Wilms瘤蛋白（WT1）是此类抗原特异性免疫治疗的有效靶点，且在DIPG和pHGG中过表达。基于此，我们设计了一项非随机I/II期试验，评估负载WT1 mRNA的DC（WT1/DC）免疫治疗联合常规治疗在pHGG和DIPG中的可行性和安全性。方法与分析：10例新诊断或经治的HGG或DIPG儿童患者按试验方案接受治疗。
弥漫性内生性脑桥胶质瘤（DIPG）和儿童高级别胶质瘤（pHGG）是侵袭性胶质肿瘤，常规治疗手段效果不佳。基于树突状细胞（DC）的免疫治疗正被研究作为一种有前景且安全的辅助疗法。Wilms瘤蛋白（WT1）是此类抗原特异性免疫治疗的有效靶点，且在DIPG和pHGG中过表达。基于此，我们设计了一项非随机I/II期试验，评估负载WT1 mRNA的DC（WT1/DC）免疫治疗联合常规治疗在pHGG和DIPG中的可行性和安全性。方法与分析：10例新诊断或经治的HGG或DIPG儿童患者按试验方案接受治疗。试验方案包括单核细胞白细胞分离术、自体WT1/DC疫苗的制备以及WT1/DC疫苗免疫治疗与常规抗胶质瘤治疗的联合。在新诊断患者中，该方案包括放化疗（口服替莫唑胺90 mg/m 2 每日+放疗54 Gy，1.8 Gy分次）后给予三剂诱导性WT1/DC疫苗（8-10×10 6 细胞/剂），每周一次，随后进入化学免疫治疗加强阶段，包括六个28天周期的口服替莫唑胺（第1-5天150-200 mg/m 2）及第21天接种一剂WT1/DC疫苗。在经治患者中，诱导期和加强期与当前最佳抗胶质瘤治疗相结合。主要目标是评估在该患者群体中生产mRNA电穿孔WT1/DC疫苗的可行性，以及评估常规抗胶质瘤治疗与所提议免疫治疗联合的安全性和可行性。次要目标是研究 WT1/DC 疫苗的体内免疫原性，并评估疾病特异性和总体生活质量。伦理与传播：安特卫普大学医院和安特卫普大学的伦理委员会已批准伦理审查。临床试验结果将通过发表在同行评审期刊和会议报告中进行分享。
INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms' tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG. METHODS AND ANALYSIS: 10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m 2 daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8-10×10 6 cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150-200 mg/m 2 on days 1-5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life. ETHICS AND DISSEMINATION: The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences. TRIAL REGISTRATION NUMBER: NCT04911621.
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