Gene therapy for malignant glioma: Current clinical status

被引:143
|
作者
Pulkkanen, KJ
Yla-Herttuala, S
机构
[1] Univ Kuopio, Dept Mol Med, AI Virtanen Inst, FIN-70211 Kuopio, Finland
[2] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland
[3] Kuopio Univ Hosp, Dept Med, SF-70210 Kuopio, Finland
[4] Kuopio Univ Hosp, Gene Therapy Unit, SF-70210 Kuopio, Finland
关键词
brain tumor; cancer; clinical trial; gene therapy; malignant glioma;
D O I
10.1016/j.ymthe.2005.07.357
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Glioblastoma is an aggressive brain tumor with a dismal prognosis. Gene therapy may offer a new option for the treatment of these patients. Several gene therapy approaches have shown anti-tumor efficiency in experimental studies, and the first clinical trials for the treatment of malignant glioma were conducted in the 1990s. HSV-tk gene therapy has been the pioneering and most commonly used approach, but oncolytic conditionally replicating adenoviruses and herpes simplex virus mutant vectors, p53, interleukins, interferons, and antisense oligonucleotides have also been used. During the past few years, adenoviruses have become the most popular gene transfer vectors, and some recent randomized, controlled trials have shown significant anti-tumor efficacy in clinical use. However, efficient gene delivery into the brain still presents a major problem, and there is a lack of definitive phase III trials, which would avoid potential problems associated with a small number of patients, inadvertent patient selection, and overinterpretation of results based on a few long-time survivors. For clinical efficacy, median survival is one of the most rigorous endpoints. It is used here to evaluate the usefulness of various treatment approaches and current clinical status of gene therapy for malignant glioma.
引用
收藏
页码:585 / 598
页数:14
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