[关键词]
[摘要]
应用病毒治疗肿瘤已有100多年的历史,随着人们对各种溶瘤病毒研究的不断深入,已能够对多种病毒进行定向操作和改造,从而改变和控制病毒的行为和功能。自1991年首次对单纯疱疹病毒1型进行基因改造以来,多种基因重组的溶瘤病毒如腺病毒及牛痘病毒等相继研制成功。至今,在全球范围内注册开展治疗肿瘤的溶瘤病毒临床试验已有百余项,有基因改造的溶瘤病毒,也有野生型或自然变异的弱毒株,涉及大多数常见的肿瘤类型。一系列的临床试验已完成,溶瘤病毒治疗肿瘤的安全性和有效性得以证实,取得了许多令人鼓舞的成果。本文追踪近年来溶瘤病毒治疗肿瘤临床试验的相关研究进展,对腺病毒、呼肠孤病毒、麻疹病毒、单纯疱疹病毒、新城疫病毒及牛痘病毒等溶瘤病毒的临床试验情况、存在问题及未来发展方向等内容进行回顾和展望。
[Key word]
[Abstract]
Viruses have been used in the treatment of cancers for more than 100 years. As the understanding of various oncolytic viruses deepens, it is more feasible to perform targeted manipulation of viral genes and thus control their behaviors and functions. Since the report of gene-modification of herpes simplex virus type 1 (HSV-1) in 1991, multi-gene recombination of oncolytic viruses (e.g. adenovirus and vaccinia virus) has been attempted. To date, more than 100 clinical trials on the application of wild-type, genetically modified or naturally mutated oncolytic viruses in cancer therapy have been registered worldwide; some of these trials have been completed while others are still ongoing. Overall, the use of oncolytic viruses for most of the common cancers evaluated has been demonstrated to be safe and encouraging clinical outcomes have been obtained. In this review paper, we attempt to outline the past achievements made from, the currently existing problems with, and the future directions and perspectives of clinical trials on oncolytic viruses in cancer therapy.
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[基金项目]
国家自然科学基金资助项目(No.81360346),贵州省科技厅社会发展攻关项目资助\[No. 黔科合SY(2012)3094号\],贵州省科技厅贵阳医学院联合基金资助项目\[No.黔科合LG字(2011)011号\]。