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首页> 外文期刊>The Open Gene Therapy Journal >Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response
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Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response

机译：靶向腺病毒进入以增强溶瘤抗肿瘤反应

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Conditionally replicative adenoviruses represent an innovative group of anticancer agents designed to destroy these cells by replication and lysis. A major problem associated with of the use of adenoviral vectors in gene therapy is its high liver uptake and lack of tumor selectivity upon systemic administration. To improve the efficacy of CRAds as anticancer agents, their infection efficiency on CAR-deficient tumor cells could be enhanced their by redirecting viral entry via a CAR-independent pathway. To redirect the entry pathway of adenoviruses and enhance their infectivity and specificity, two general strategies are being used. In the first strategy, the adenovirus genome is changed to alter the binding specificity of the viral capsid. In the second strategy, a two-component targeted adenovirus is created by binding of proteins with specific affinity for cancer cells onto the viral capsid. Despite effective targeting and tumor eradication in vitro and in mouse models, the results from systemic administration of targeted CrAds is limited. In addition, clinical effects of CrAds are disappointing up till now. Therefore, combination therapies in which targeted CrAds are combined with other types of therapy are being investigated.
机译：有条件复制的腺病毒代表一组创新的抗癌药，旨在通过复制和裂解来破坏这些细胞。在基因治疗中使用腺病毒载体相关的主要问题是其高肝吸收和全身给药后缺乏肿瘤选择性。为了提高CRAds作为抗癌药的功效，可以通过不依赖CAR的途径重定向病毒进入，从而提高其对CAR缺陷型肿瘤细胞的感染效率。为了重定向腺病毒的进入途径并增强其感染性和特异性，正在使用两种通用策略。在第一种策略中，改变腺病毒基因组以改变病毒衣壳的结合特异性。在第二种策略中，通过将对癌细胞具有特定亲和力的蛋白质结合到病毒衣壳上，来创建靶向两组分的腺病毒。尽管在体外和小鼠模型中有效靶向和消灭肿瘤，但是全身施用靶向CrAds的结果仍然有限。此外，到目前为止，CrAds的临床效果令人失望。因此，正在研究将靶向的CrAd与其他类型的疗法组合的组合疗法。

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