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肿瘤渗漏:利用产气荚膜梭菌穿孔毒素(CPE)进行自杀基因治疗

Oncoleaking: Use of the Pore-Forming Clostridium perfringens Enterotoxin (CPE) for Suicide Gene Therapy.

作者信息

Pahle Jessica, Aumann Jutta, Kobelt Dennis, Walther Wolfgang

机构信息

Experimental and Clinical Research Center (ECRC), Charité University Medicine Berlin, Berlin, Germany.

出版信息

Methods Mol Biol. 2015;1317:69-85. doi: 10.1007/978-1-4939-2727-2_5.

Abstract

Suicide gene therapy has been shown to be very efficient in tumor eradication. Numerous suicide genes were tested in vitro and in vivo demonstrating their therapeutic potential in clinical trials. Apart from this, still growing efforts are made to generate more targeted and more effective suicide gene systems for cancer gene therapy. In this regard bacterial toxins are an alternative, which add to the broad spectrum of different suicide strategies. In this context, the claudin-targeted bacterial Clostridium perfringens enterotoxin (CPE) is an attractive new type of suicide oncoleaking gene, which as pore-forming protein exerts specific and rapid toxicity towards claudin-3- and -4-overexpressing cancers. In this chapter we describe the generation and use of CPE-expressing vectors for the effective tumor cell killing as novel suicide gene approach particularly for treatment of therapy refractory tumors.

摘要

自杀基因疗法已被证明在根除肿瘤方面非常有效。众多自杀基因在体外和体内进行了测试,显示出它们在临床试验中的治疗潜力。除此之外,人们仍在不断努力,以开发出更具靶向性和更有效的用于癌症基因治疗的自杀基因系统。在这方面,细菌毒素是一种选择,它丰富了不同自杀策略的范围。在此背景下,靶向紧密连接蛋白的产气荚膜梭菌肠毒素(CPE)是一种有吸引力的新型自杀性肿瘤渗漏基因,作为一种成孔蛋白,它对过表达紧密连接蛋白3和4的癌症具有特异性和快速毒性。在本章中,我们描述了表达CPE的载体的构建及其用于有效杀伤肿瘤细胞的用途,这是一种新型自杀基因方法,尤其适用于治疗难治性肿瘤。

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