Amara Ikrame, Touati Walid, Beaune Philippe, de Waziers Isabelle
INSERM UMR-S 1147, Paris Descartes University, Sorbonne Paris Cité, 45 rue des Saints Pères, 75006 Paris, France.
INSERM UMR-S 1147, Paris Descartes University, Sorbonne Paris Cité, 45 rue des Saints Pères, 75006 Paris, France.
Biochimie. 2014 Oct;105:4-11. doi: 10.1016/j.biochi.2014.06.016. Epub 2014 Jun 27.
Gene-directed enzyme prodrug therapy (GDEPT) consists of targeted delivery to tumor cells of a suicide gene responsible for the in situ conversion of a prodrug into cytotoxic metabolites. One of the major impediments of GDEPT is to target specifically the tumor cells with the suicide gene. Among gene delivery methods, mesenchymal stem cells (MSCs) have emerged recently as potential cellular vehicles for gene delivery. MSCs are particularly suited for gene transduction. They exhibit remarkable migratory property towards tumors and their metastases and they are weakly immunogenic. This review will summarize the current knowledge about MSCs engineered to express different suicide genes (cytosine deaminase, thymidine kinase, carboxylesterase, cytochrome P450) to elicit a significant antitumor response against brain tumors, ovarian, hepatocellular, pancreatic, renal or medullary thyroid carcinomas, breast or prostate cancer and pulmonary metastases. The potential side effects of these MSC-based tumor therapies will also be considered to highlight certain aspects that need to be improved prior to clinical use.
基因导向酶前药疗法（GDEPT）包括将负责将前药原位转化为细胞毒性代谢物的自杀基因靶向递送至肿瘤细胞。GDEPT的主要障碍之一是用自杀基因特异性靶向肿瘤细胞。在基因递送方法中，间充质干细胞（MSCs）最近已成为基因递送的潜在细胞载体。间充质干细胞特别适合基因转导。它们对肿瘤及其转移灶表现出显著的迁移特性，并且免疫原性较弱。本综述将总结目前关于经工程改造以表达不同自杀基因（胞嘧啶脱氨酶、胸苷激酶、羧酸酯酶、细胞色素P450）的间充质干细胞的知识，这些自杀基因可引发针对脑肿瘤、卵巢癌、肝细胞癌、胰腺癌、肾癌或甲状腺髓样癌、乳腺癌或前列腺癌以及肺转移瘤的显著抗肿瘤反应。还将考虑这些基于间充质干细胞的肿瘤疗法的潜在副作用，以突出在临床应用前需要改进的某些方面。
