Both Gerald W
Biotech Equity Partners, NSW, Australia.
Curr Opin Mol Ther. 2009 Aug;11(4):421-32.
The principle of gene-directed enzyme prodrug therapy (GDEPT) has existed for many years but, while simple in concept, the effective practical application of this therapy has proven to be challenging. Improvements in the efficacy of GDEPT have been achieved principally through the choice and development of more effective vectors, by optimizing and controlling gene expression and by increasing the activity of the delivered enzyme through mutation. While innovation continues in this field, the pioneering GDEPT systems designed to treat glioma and prostate cancer have completed or are now entering late-stage clinical trials, respectively. As the pace of innovation in GDEPT technology far exceeds its clinical application, these initial products are anticipated to be replaced by next-generation biologicals. This review highlights recent progress in the strategies and development of GDEPT and summarizes the status of current clinical trials. With the first GDEPT product for treatment of resected gliomas poised to gain marketing approval, a new era in cancer gene medicine is emerging.
基因导向酶前药疗法（GDEPT）的原理已存在多年，虽然概念简单，但事实证明，这种疗法的有效实际应用具有挑战性。GDEPT疗效的提高主要通过选择和开发更有效的载体、优化和控制基因表达以及通过突变提高所递送酶的活性来实现。尽管该领域的创新仍在继续，但旨在治疗神经胶质瘤和前列腺癌的开创性GDEPT系统已分别完成或正在进入后期临床试验。由于GDEPT技术的创新步伐远远超过其临床应用，预计这些初始产品将被下一代生物制品所取代。本综述重点介绍了GDEPT策略和开发方面的最新进展，并总结了当前临床试验的状况。随着首款用于治疗切除的神经胶质瘤的GDEPT产品有望获得上市批准，癌症基因医学的新时代正在兴起。
