Greco O, Dachs G U
Tumour Microcirculation Group, Gray Laboratory Cancer Research Trust, Mount-Verion Hospital, Northwood, Middlesex, UK.
J Cell Physiol. 2001 Apr;187(1):22-36. doi: 10.1002/1097-4652(2001)9999:9999<::AID-JCP1060>3.0.CO;2-H.
Gene therapy of cancer is a novel approach with the potential to selectively eradicate tumour cells, whilst sparing normal tissue from damage. In particular, gene-directed enzyme prodrug therapy (GDEPT) is based on the delivery of a gene that encodes an enzyme which is non-toxic per se, but is able to convert a prodrug into a potent cytotoxin. Several GDEPT systems have been investigated so far, demonstrating effectiveness in both tissue culture and animal models. Based on these encouraging results, phase I/II clinical trials have been performed and are still ongoing. The aim of this review is to summarise the progress made in the design and application of GDEPT strategies. The most widely used enzyme/prodrug combinations already in clinical trials (e.g., herpes simplex 1 virus thymidine kinase/ganciclovir and cytosine deaminase/5-fluorocytosine), as well as novel approaches (carboxypeptidase G2/CMDA, horseradish peroxidase/indole-3-acetic acid) are described, with a particular attention to translational research and early clinical results.
癌症基因治疗是一种新型方法，有潜力选择性地根除肿瘤细胞，同时使正常组织免受损伤。特别是，基因导向酶前药疗法（GDEPT）基于递送一种编码酶的基因，该酶本身无毒，但能够将前药转化为强效细胞毒素。到目前为止，已经研究了几种GDEPT系统，在组织培养和动物模型中均显示出有效性。基于这些令人鼓舞的结果，已经开展了I/II期临床试验，并且仍在进行中。本综述的目的是总结GDEPT策略在设计和应用方面取得的进展。文中描述了已在临床试验中使用最广泛的酶/前药组合（例如，单纯疱疹病毒1型胸苷激酶/更昔洛韦和胞嘧啶脱氨酶/5-氟胞嘧啶）以及新方法（羧肽酶G2/CMDA、辣根过氧化物酶/吲哚-3-乙酸），特别关注转化研究和早期临床结果。
