Reale Alberto, Calistri Arianna, Altomonte Jennifer
Department of Molecular Medicine, University of Padua, 35121 Padua, Italy.
Department of Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
Pharmaceutics. 2021 Dec 18;13(12):2192. doi: 10.3390/pharmaceutics13122192.
Oncolytic viruses (OVs) are an emerging class of therapeutics which combine multiple mechanisms of action, including direct cancer cell-killing, immunotherapy and gene therapy. A growing number of clinical trials have indicated that OVs have an excellent safety profile and provide some degree of efficacy, but to date only a single OV drug, HSV-1 talimogene laherparepvec (T-Vec), has achieved marketing approval in the US and Europe. An important issue to consider in order to accelerate the clinical advancement of OV agents is the development of an effective delivery system. Currently, the most commonly employed OV delivery route is intratumoral; however, to target metastatic diseases and tumors that cannot be directly accessed, it is of great interest to develop effective approaches for the systemic delivery of OVs, such as the use of carrier cells. In general, the ideal carrier cell should have a tropism towards the tumor microenvironment (TME), and it must be susceptible to OV infection but remain viable long enough to allow migration and finally release of the OV within the tumor bed. Mesenchymal stem cells (MSCs) have been heavily investigated as carrier cells due to their inherent tumor tropism, in spite of some disadvantages in biodistribution. This review focuses on the other promising candidate carrier cells under development and discusses their interaction with specific OVs and future research lines.
溶瘤病毒（OVs）是一类新兴的治疗药物，它结合了多种作用机制，包括直接杀死癌细胞、免疫治疗和基因治疗。越来越多的临床试验表明，溶瘤病毒具有良好的安全性，并具有一定程度的疗效，但迄今为止，只有一种溶瘤病毒药物，即单纯疱疹病毒1型塔利莫基因拉帕利韦克（T-Vec），在美国和欧洲获得了上市批准。为了加速溶瘤病毒制剂的临床进展，需要考虑的一个重要问题是开发一种有效的递送系统。目前，最常用的溶瘤病毒递送途径是瘤内注射；然而，为了靶向转移性疾病和无法直接触及的肿瘤，开发溶瘤病毒全身递送的有效方法，如使用载体细胞，具有重要意义。一般来说，理想的载体细胞应该对肿瘤微环境（TME）具有嗜性，并且必须易于被溶瘤病毒感染，但要存活足够长的时间，以允许其迁移并最终在肿瘤床内释放溶瘤病毒。间充质干细胞（MSCs）因其固有的肿瘤嗜性而被大量研究作为载体细胞，尽管其在生物分布方面存在一些缺点。本综述重点关注正在开发的其他有前景的候选载体细胞，并讨论它们与特定溶瘤病毒的相互作用以及未来的研究方向。
