Cancer Suicide Gene Therapy with TK.007
Cancer Suicide Gene Therapy with TK.007
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DOI：
10.1007/978-1-4939-8922-5_2
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Fehse, Boris
中科院分区：
文献类型：
--
作者：
Hossain, Jubayer A.;Riecken, Kristoffer;Fehse, Boris
癌症是一种毁灭性的疾病，其特征是细胞生长不受控制且具有侵袭性。自杀基因治疗(SGT)有助于诱导恶性肿瘤特异性细胞死亡，是一种治疗癌症的新方法，已在几种癌症类型中进行了研究，取得了非常有希望的结果。此外，SGT已被认为是过继免疫治疗和再生医学环境中的一种保障措施。一般说来，SGT包括两个步骤--载体介导的自杀基因进入肿瘤和随后激活自杀机制，例如通过给予特定的前药。本章提供了使用单纯疱疹病毒胸苷激酶(HSV-TK)/更昔洛韦(GCV)系统进行基础研究和翻译研究的协议框架，HSV-TK/GCV是最广泛使用的自杀基因方法。这些方案为编码经基因改良的HSV-TK版本TK.007的高滴度第三代慢病毒载体的制备及其在体外和体内治疗装置中的应用提供了标准指南。
Cancer is a devastating disease characterized by uncontrolled and aggressive cell growth. Suicide gene therapy (SGT) facilitating induction of malignancy-specific cell death represents a novel therapeutic approach to treat cancer, which has been investigated in several cancer types with very promising results. In addition, SGT has been suggested as a safeguard in adoptive immunotherapy and regenerative-medicine settings. Generally, SGT consists of two steps-vector-mediated delivery of suicide genes into tumors and subsequent activation of the suicide mechanism, e.g., by administration of a specific prodrug. This chapter provides a framework of protocols for basic and translational research using the Herpes-simplex-virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system, the most widely used suicide gene approach. The protocols provide standard guidelines for the preparation of high-titer third-generation lentiviral vectors encoding a genetically improved HSV-TK version known as TK.007 and its application in in vitro and in vivo treatment setups.