Goradel Nasser Hashemi, Negahdari Babak, Ghorghanlu Sajjad, Jahangiri Samira, Arashkia Arash
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Pharmacol Ther. 2020 Sep;213:107586. doi: 10.1016/j.pharmthera.2020.107586. Epub 2020 May 30.
Oncolytic viruses, effectively replicate viruses within malignant cells to lyse them without affecting normal ones, have recently shown great promise in developing therapeutic options for cancer. Adenoviruses (Ads) are one of the candidates in oncolytic virotheraoy due to its easily manipulated genomic DNA and expression of wide rane of its receptors on the various cancers. Although systematic delivery of oncolytic adenoviruses can target both primary and metastatic tumors, there are some drawbacks in the effective systematic delivery of oncolytic adenoviruses, including pre-existing antibodies and liver tropism. To overcome these limitations, intratumural (IT) administration of oncolytic viruses have been proposed. However, IT injection of Ads leaves much of the tumor mass unaffected and Ads are not able to disperse more in the tumor microenvironment (TME). To this end, various strategies have been developed to enhance the IT spread of oncolytic adenoviruses, such as using extracellular matrix degradation enzymes, junction opening peptides, and fusogenic proteins. In the present paper, we reviewed different oncolytic adenoviruses, their application in the clinical trials, and strategies for enhancing their IT spread.
溶瘤病毒能在恶性细胞内有效复制病毒以裂解这些细胞，而不影响正常细胞，最近在开发癌症治疗方案方面显示出巨大潜力。腺病毒因其易于操作的基因组DNA以及其受体在多种癌症上广泛表达，是溶瘤病毒疗法的候选病毒之一。尽管系统性递送溶瘤腺病毒可靶向原发性和转移性肿瘤，但在溶瘤腺病毒的有效系统性递送方面存在一些缺点，包括预先存在的抗体和肝嗜性。为克服这些限制，已提出瘤内（IT）注射溶瘤病毒。然而，瘤内注射腺病毒会使大部分肿瘤组织未受影响，且腺病毒无法在肿瘤微环境（TME）中进一步扩散。为此，已开发出各种策略来增强溶瘤腺病毒的瘤内扩散，例如使用细胞外基质降解酶、连接开放肽和融合蛋白。在本文中，我们综述了不同的溶瘤腺病毒、它们在临床试验中的应用以及增强其瘤内扩散的策略。
