Kew Yvonne, Levin Victor A
Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.
Curr Opin Neurol. 2003 Dec;16(6):665-70. doi: 10.1097/01.wco.0000102625.38669.62.
Treatments for malignant glioma, the most lethal and common primary brain tumor, are undergoing a dramatic evolution led by biological and technological advancements. This review focuses on developments in novel areas of gene therapy and immunotherapy, particularly vaccine development.
Advances in basic research of antigen-presenting cells and applications of cytokines and immunogenic antigens have contributed to recent vaccine development for the treatment of intracranial malignant glioma. We have reviewed various vaccine designs, such as utilization of tumor antigen-loaded dendritic cells. Many immunotherapeutic manipulations require the use of recombinant genetic technologies. Here we present the findings on improved techniques for suicide gene therapy and various oncolytic viral therapies. Some of these constructs have induced an immune response at tumor sites in animal models of glioma.
The intense investigation of therapies for glioma has made significant advances in designing diverse therapies with great potential. However, vaccine development has been hampered by the lack of universal tumor-specific antigens and a limited understanding of the mechanisms of tumor-induced immunosuppression. The success of gene therapy is limited by ineffective delivery systems and possible risk of infecting normal cells. As a result of the genetic heterogeneity of glioma cells and their invasive nature, future treatment approaches are likely to combine different agents in synergistic strategies that will hopefully be successful in stopping the growth and recurrence of glioma.
恶性胶质瘤是最致命且常见的原发性脑肿瘤，其治疗方法正经历由生物学和技术进步引领的巨大变革。本综述聚焦于基因治疗和免疫治疗新领域的进展，尤其是疫苗研发。
抗原呈递细胞基础研究的进展以及细胞因子和免疫原性抗原的应用推动了近期用于治疗颅内恶性胶质瘤的疫苗研发。我们回顾了多种疫苗设计，如利用负载肿瘤抗原的树突状细胞。许多免疫治疗操作需要使用重组基因技术。在此，我们展示自杀基因治疗和各种溶瘤病毒治疗改进技术的研究结果。其中一些构建体在胶质瘤动物模型的肿瘤部位诱导了免疫反应。
对胶质瘤治疗的深入研究在设计具有巨大潜力的多种治疗方法方面取得了重大进展。然而，疫苗研发因缺乏通用的肿瘤特异性抗原以及对肿瘤诱导免疫抑制机制的了解有限而受阻。基因治疗的成功受到无效递送系统以及感染正常细胞的潜在风险的限制。由于胶质瘤细胞的基因异质性及其侵袭性，未来的治疗方法可能会将不同药物以协同策略组合起来，有望成功阻止胶质瘤的生长和复发。
