Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Mol Ther. 2009 Oct;17(10):1667-76. doi: 10.1038/mt.2009.194. Epub 2009 Aug 18.
Oncolytic viruses delivered directly into the circulation face many hazards that impede their localization to, and infection of, metastatic tumors. Such barriers to systemic delivery could be overcome if couriers, which confer both protection, and tumor localization, to their viral cargoes, could be found. Several preclincal studies have shown that viruses can be loaded into, or onto, different types of cells without losing the biological activity of either virus or cell carrier. Importantly, such loading can significantly protect the viruses from immune-mediated virus-neutralizing activities, including antiviral antibody. Moreover, an impressive portfolio of cellular vehicles, which have some degree of tropism for tumor cells themselves, or for the biological properties associated with the tumor stroma, is already available. Therefore, it will soon be possible to initiate clinical protocols to test the hypopthesis that cell-mediated delivery can permit efficient shipping of oncolytic viruses from the loading bay (the production laboratory) directly to the tumor in immune-competent patients with metastatic disease.
直接递送至循环系统中的溶瘤病毒面临着许多阻碍其定位于转移瘤并感染转移瘤的危险。如果能够找到能够赋予其病毒货物保护和肿瘤定位能力的载体，那么全身性递送的这些障碍就可以克服。几项临床前研究表明，可以将病毒装载到或装载到不同类型的细胞中，而不会降低病毒或细胞载体的生物活性。重要的是，这种装载可以显著保护病毒免受免疫介导的病毒中和活性的影响，包括抗病毒抗体。此外，已经有大量具有一定程度对肿瘤细胞本身或与肿瘤基质相关的生物学特性的细胞载体可供使用。因此，很快就可以启动临床方案来测试这样的假设，即细胞介导的递送可以允许将溶瘤病毒从装载区（生产实验室）直接有效地运送到免疫功能正常的转移性疾病患者的肿瘤中。
