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The role of HSV amplicon vectors in cancer genetherapy

机译：HSV扩增子载体在癌症基因治疗中的作用

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Summary Recent progress in tumor biology, virology and immunology has led to new approaches to the gene therapy for cancer. Herpes Simplex Virus (HSV) based vectors are attractive vectors for gene therapy use due to a number of favorable biologic features. Several characteristics render HSV suitable for gene therapy, including high transduction efficiency, ability to transduce non-dividing cells, high packaging capacity, wide cellular tropism and the ability to package multiple copies of the same gene or several genes. Newer HSV vectors differ in replication potential, sensitivity to anti-viral agents, neurotoxicity, tumor-specific cytotoxicity and persistence in the host cell. So- called “oncolytic” HSV based vectors demonstrate selective replication in tumor cells relative to normal tissue. HSV amplicon based vectors allow genetic transfer of multiple transgene copies in the absence of viral genes. This degree of flexibility, relative to other viral vector systems, has allowed for the use of HSV vectors in a variety of antitumor strategies including oncolytic, as well as immune-based strategies. Successful immune based strategies in animal models have included transfer of cytokines, costimulatory molecules and/or chemokines. Phase I/II clinical trials usingHSV based vectors have been initiated.
机译：总结肿瘤生物学，病毒学和免疫学方面的最新进展已导致癌症基因治疗的新方法。由于许多有利的生物学特性，基于单纯疱疹病毒（HSV）的载体是用于基因治疗的有吸引力的载体。 HSV的几个特性使其适用于基因治疗，包括高转导效率，转导非分裂细胞的能力，高包装能力，宽泛的细胞嗜性以及包装同一基因或几个基因的多个拷贝的能力。较新的HSV载体在复制潜力，对抗病毒剂的敏感性，神经毒性，肿瘤特异性细胞毒性和在宿主细胞中的持久性方面有所不同。所谓的“溶瘤的”基于HSV的载体表现出相对于正常组织在肿瘤细胞中的选择性复制。基于HSV扩增子的载体可在无病毒基因的情况下进行多个转基因拷贝的遗传转移。相对于其他病毒载体系统，这种程度的灵活性已使HSV载体可用于多种抗肿瘤策略，包括溶瘤和基于免疫的策略。在动物模型中成功的基于免疫的策略包括细胞因子，共刺激分子和/或趋化因子的转移。已经开始使用基于HSV的载体进行I / II期临床试验。

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