Arming viruses in multi-mechanistic oncolytic viral therapy: current research and future developments, with emphasis on poxviruses.

IF 6.7 Oncolytic Virotherapy Pub Date : 2013-12-05 eCollection Date: 2014-01-01 DOI:10.2147/OV.S36703
Padma Sampath, Steve H Thorne
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引用次数: 8

Abstract

The field of oncolytic virology has made great strides in recent years. However, one key finding has been that the use of viral agents that replicate selectively in tumors is usually insufficient to achieve anything beyond small and transient responses. Instead, like most cancer therapies, oncolytic viruses are most effective in combination with other therapies, which is where they have proven therapeutic effects in clinical and preclinical studies. In cases of some of the smaller RNA viruses, effects can only be achieved through combination regimens with chemotherapy, radiotherapy, or targeted conventional therapies. However, larger DNA viruses are able to express one or more transgenes; thus, therapeutic mechanisms can be built into the viral vector itself. The incorporated approaches into arming oncolytic viruses through transgene expression will be the main focus of this review, including use of immune activators, prodrug converting enzymes, anti-angiogenic factors, and targeting of the stroma. This will focus on poxviruses as model systems with large cloning capacities, which have routinely been used as transgene expression vectors in different settings, including vaccine and oncolytic viral therapy.

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多机制溶瘤病毒治疗中的武装病毒:当前研究和未来发展,重点是痘病毒。
近年来,溶瘤病毒学研究取得了长足的进步。然而,一个关键的发现是,使用在肿瘤中选择性复制的病毒制剂通常不足以实现小而短暂的反应。相反,像大多数癌症疗法一样,溶瘤病毒在与其他疗法联合使用时最有效,这是它们在临床和临床前研究中证明的治疗效果。对于一些较小的RNA病毒,只能通过联合化疗、放疗或靶向常规疗法来达到效果。然而,较大的DNA病毒能够表达一种或多种转基因;因此,治疗机制可以建立在病毒载体本身。通过转基因表达武装溶瘤病毒的综合方法将是本综述的主要重点,包括使用免疫激活剂、前药转化酶、抗血管生成因子和靶向基质。这将侧重于痘病毒作为具有大克隆能力的模型系统,它通常被用作不同环境中的转基因表达载体,包括疫苗和溶瘤病毒治疗。
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