Roy Dominic Guy, Bell John Cameron, Bourgeois-Daigneault Marie-Claude
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, 501 Smyth Rd, Ottawa, Ontario, K1H 8L6, Canada; Department of Biochemistry Microbiology and Immunology University of Ottawa, 451 Smyth Rd, Ottawa, Ontario, K1H 8M5, Canada.
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, 501 Smyth Rd, Ottawa, Ontario, K1H 8L6, Canada; Department of Biochemistry Microbiology and Immunology University of Ottawa, 451 Smyth Rd, Ottawa, Ontario, K1H 8M5, Canada.
Biochem Biophys Res Commun. 2020 Jun 4;526(3):641-646. doi: 10.1016/j.bbrc.2020.03.135. Epub 2020 Apr 2.
Oncolytic viruses (OVs) are a class of biotherapeutics that are currently being explored for the treatment of cancer. While showing promise in several pre-clinical and clinical studies, systemic delivery of these anti-cancer agents is hampered by inefficient tumor targeting and a host immune system that is highly evolved to detect and neutralize pathogens. To shield the virus from immune recognition and destruction, the use of cells as delivery vehicles has been explored for the systemic delivery of OVs. Though several types of cell carriers are able to protect OVs during intravenous delivery, many still lack the ability to specifically home to or accumulate within the tumor microenvironment. Overall, OV-based therapeutics could benefit from tumor targeting strategies to maximize tumor-specific delivery and minimize infection of off-target tissues. In the current study, we examine magnetic targeting as a strategy to improve OV infection of tumor cells in vitro. We found that magnetic targeting of magnetically-labeled VSV particles or VSV-infected cell carriers resulted in increased infection and killing of tumor cells. Furthermore, this enhanced infection of target tumor cells was observed even in the presence of virus-specific neutralizing antibodies. Overall, our findings suggest that magnetic targeting strategies can improve the infection of tumor cells and may be a viable strategy to improve the tumor-targeted delivery of oncolytic VSV-based therapeutics.
溶瘤病毒（OVs）是一类目前正在探索用于癌症治疗的生物疗法。尽管在一些临床前和临床研究中显示出前景，但这些抗癌药物的全身递送受到肿瘤靶向效率低下以及高度进化以检测和中和病原体的宿主免疫系统的阻碍。为了使病毒免受免疫识别和破坏，人们探索了使用细胞作为递送载体来进行溶瘤病毒的全身递送。尽管几种类型的细胞载体能够在静脉内递送过程中保护溶瘤病毒，但许多载体仍然缺乏特异性归巢到肿瘤微环境或在其中积累的能力。总体而言，基于溶瘤病毒的疗法可受益于肿瘤靶向策略，以最大限度地实现肿瘤特异性递送并最小化非靶组织的感染。在当前的研究中，我们研究了磁靶向作为一种在体外改善溶瘤病毒对肿瘤细胞感染的策略。我们发现对磁性标记的水疱性口炎病毒（VSV）颗粒或VSV感染的细胞载体进行磁靶向会导致肿瘤细胞的感染和杀伤增加。此外，即使在存在病毒特异性中和抗体的情况下，也观察到靶肿瘤细胞的这种增强感染。总体而言，我们的研究结果表明磁靶向策略可以改善肿瘤细胞的感染，并且可能是一种可行的策略来改善基于溶瘤VSV的疗法的肿瘤靶向递送。
