基于多效生长因子的神经胶质母细胞瘤治疗性疫苗的设计与评价

神经胶质母细胞瘤是恶性程度最高的颅内肿瘤，即使通过手术，放化疗等综合治疗，该病病人的存活时间仍然只有12-15个月，且该肿瘤的疗效和预后在近30年来也并未有根本改变。本研究拟设计制备一种全新的神经胶质瘤治疗性疫苗，该疫苗以以多效生长因子（pleiotrophin，PTN）为靶点。疫苗是由外源蛋白与内源蛋白（PTN）构成的融合蛋白，利用此融合蛋白打破体内自身免疫耐受机制，诱导体内产生特异性PTN抗体，启动免疫反应，中和体内的PTN，从而抑制肿瘤生长。本研究还将筛选可用于人体安全高效的免疫佐剂，为后续应用于临床打下基础。该疫苗将在两种神经胶质母细胞瘤小鼠模型中进行测试，确定其抗肿瘤作用，并揭示作用机制。本项研究将为神经胶质母细胞瘤的治疗提供副作用小，特异性高的全新策略。

Glioblastoma is the most aggressive type of brain tumors. Despite of the maximum surgical resection plus chemotherapy and radiotherapy post-surgery, the survival for the patients is only 12-15 months, and has not been improved substantially for last 30 years. Here, we design a novel therapeutic vaccine for treating glioblastoma. The vaccine is a fusion protein containing self-antigen (PTN) and non-self-antigen, which will break the self-tolerance and leads to production of anti-PTN antibody with high efficiency. By neutralizing PTN in the circulation and in tumor, tumor progression will be attenuated. In this proposal, we will also screen for bio-degradable adjuvant with high efficiency and can be used for human. By employing the vaccine in two glioblastoma mouse models, we expect to assess its anti-tumor effect and to uncover the mechanisms behind. This research will provide a novel treatment for glioblastoma with high specificity and much less side effect.