Virotherapy and immunotherapy group, ProCURE Program, Catalan Institute of Oncology - ICO, L'Hospitalet de Llobregat, Spain
Cancer Virotherapy group, Oncobell Program, Institutd'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain.
J Immunother Cancer. 2021 Feb;9(2). doi: 10.1136/jitc-2020-001684.
The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic 'cold' tumors into inflamed immunogenic 'hot' tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.
在过去的 20 年中，溶瘤病毒（OVs）的发展有了显著的提高，许多候选药物已进入临床试验，其中有三种药物已获准用于某些适应症。最近，由于其免疫原性，OVs 也被作为免疫疗法联合应用于癌症治疗的候选药物，这些免疫原性包括免疫原性细胞死亡和在其基因组中携带治疗性转基因的可能性。OVs 将非免疫原性的“冷”肿瘤转化为炎症免疫原性的“热”肿瘤，免疫疗法在这种肿瘤中显示出最高的疗效。然而，在单独使用或与免疫疗法联合使用时，OVs 面临着许多限制其成功应用的挑战，特别是在全身给药时，如肝脏隔离、血液中的中和作用、感染的物理屏障以及免疫系统的快速清除。在这方面，使用间充质干细胞（MSCs）作为 OV 递送的细胞载体，可作为病毒载体和工厂，表达额外的转基因，并调节免疫系统，从而解决了其中的许多障碍。在此，我综述了负载 OV 的 MSC 在癌症中的最新进展，重点讨论了它们与免疫系统的相互作用，并讨论了提高其治疗效果的新策略。
