Todo Tomoki
Molecular Neurosurgery Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Hum Cell. 2002 Sep;15(3):151-9. doi: 10.1111/j.1749-0774.2002.tb00109.x.
An increasing number of oncolytic virus vectors has been developed lately for cancer therapy. Herpes simplex virus type 1 (HSV-1) vectors are particularly useful, because they can be genetically engineered to replicate and spread highly selectively in tumor cells and can also express multiple foreign transgenes. These vectors can manifest cytopathic effect in a wide variety of tumor types without damaging normal tissues, provide amplified gene delivery within the tumor, and induce specific antitumor immunity. Multiple recombinant HSV-1 vectors have been tested in patients with brain tumors and other cancers, which showed the feasibility of administering replication-competent HSV-1 vectors safely in human organs including the brain. Different approaches are currently undertaken to improve the efficacy of oncolytic HSV-1 therapy which include development of new generation vectors via further genetic engineering of existing safe vectors, combination with immune gene therapy, and combination with conventional therapies. Oncolytic virus therapy is a promising therapeutic modality that awaits establishing as an important treatment option for cancer patients in the near future.
近年来,越来越多的溶瘤病毒载体被开发用于癌症治疗。1型单纯疱疹病毒(HSV-1)载体尤为有用,因为它们可以通过基因工程改造,在肿瘤细胞中高度选择性地复制和传播,还能表达多个外源转基因。这些载体可在多种肿瘤类型中表现出细胞病变效应,而不损害正常组织,在肿瘤内实现基因递送扩增,并诱导特异性抗肿瘤免疫。多种重组HSV-1载体已在脑肿瘤和其他癌症患者中进行了测试,结果表明在包括脑在内的人体器官中安全施用具有复制能力的HSV-1载体是可行的。目前正在采取不同方法来提高溶瘤HSV-1疗法的疗效,包括通过对现有安全载体进行进一步基因工程开发新一代载体、与免疫基因疗法联合以及与传统疗法联合。溶瘤病毒疗法是一种很有前景的治疗方式,有望在不久的将来成为癌症患者的重要治疗选择。