Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland; Institute of Chemistry, University of Silesia, Poland.
Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland.
Eur J Pharmacol. 2020 May 5;874:172991. doi: 10.1016/j.ejphar.2020.172991. Epub 2020 Feb 7.
Progress in genetic engineering led to the emergence of some viruses as potent anticancer therapeutics. These oncolytic viruses combine self-amplification with dual antitumor action: oncolytic (destruction of cancer cells) and immunostimulatory (eliciting acquired antitumor response against cancer epitopes). As any other viruses, they trigger antiviral response upon systemic administration. Mesenchymal stem cells are immature cells capable of self-renewing and differentiating into many cell types that belong to three germinal layers. Due to their inherent tumor tropism mesenchymal stem cells loaded with oncolytic virus can improve delivery of the therapeutic cargo to cancer sites. Shielding of oncolytic viral construct from antiviral host immune response makes these cells prospective delivery vehicles to even hard-to-reach metastatic neoplastic foci. Use of mesenchymal stem cells has been criticized by some investigators as limiting proliferative abilities of primary cells and increasing the risk of malignant transformation, as well as attenuating therapeutic responses. However, majority of preclinical studies indicate safety and efficacy of mesenchymal stem cells used as carriers of oncolytic viruses. In view of contradictory postulates, the debate continues. The review discusses mesenchymal stem cells as carriers for delivery of genetically engineered oncolytic constructs and focuses on systemic approach to oncoviral treatment of some deadly neoplasms.
基因工程的进展导致一些病毒作为有效的抗癌治疗药物出现。这些溶瘤病毒将自我扩增与双重抗肿瘤作用相结合：溶瘤（破坏癌细胞）和免疫刺激（引发针对癌症表位的获得性抗肿瘤反应）。与任何其他病毒一样，它们在全身给药时会引发抗病毒反应。间充质干细胞是不成熟的细胞，能够自我更新并分化为属于三个胚层的许多细胞类型。由于其固有的肿瘤趋向性，负载溶瘤病毒的间充质干细胞可以改善治疗货物向癌症部位的递送。溶瘤病毒构建体的抗病毒宿主免疫反应的屏蔽使这些细胞成为即使是难以到达的转移性肿瘤焦点的有前途的递送载体。一些研究人员批评使用间充质干细胞，因为它限制了原代细胞的增殖能力，并增加了恶性转化的风险，同时也减弱了治疗反应。然而，大多数临床前研究表明，使用间充质干细胞作为溶瘤病毒载体是安全有效的。鉴于相互矛盾的假设，争论仍在继续。本文讨论了间充质干细胞作为基因工程溶瘤构建体递送载体的作用，并重点介绍了全身性方法治疗某些致命性肿瘤。
