Podshivalova Elizaveta Sergeevna, Semkina Alevtina Sergeevna, Kravchenko Dmitry Sergeevich, Frolova Elena Ivanovna, Chumakov Stepan Petrovich
Department of Peptide and Protein Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117997, Russia.
Department of Medical Nanobiotechnologies, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia.
Mol Ther Oncolytics. 2021 Apr 1;21:110-118. doi: 10.1016/j.omto.2021.03.013. eCollection 2021 Jun 25.
Many members of the enterovirus family are considered as promising oncolytic agents; however, their systemic administration is largely inefficient due to the rapid neutralization of the virus in the circulation and the barrier functions of the endothelium. We aimed to evaluate natural killer cells as carriers for the delivery of oncolytic enteroviruses, which would combine the effects of cell immunotherapy with virotherapy. We tested four strains of nonpathogenic enteroviruses against the glioblastoma cell line panel and evaluated the produced infectious titers. Next, we explored whether these virus strains could be delivered to the tumor by natural killer cell line NK-92, which is being actively evaluated as a clinically acceptable therapeutic. Several strains of enteroviruses demonstrated oncolytic properties, but only coxsackievirus A7 (CVA7) could replicate in NK-92 cells efficiently. We compared the delivery efficiency of CVA7 , using NK-92 cells and direct intravenous administration, and found significant advantages of cell delivery even after a single injection. This suggests that the NK-92 cell line can be utilized as a vehicle for the delivery of the oncolytic strain of CVA7, which would improve the clinical potential of this viral oncolytic for the treatment of glioblastoma multiforme and other forms of cancer.
肠道病毒家族的许多成员被认为是有前景的溶瘤剂；然而，由于病毒在循环系统中迅速被中和以及内皮细胞的屏障功能，它们的全身给药效率很低。我们旨在评估自然杀伤细胞作为溶瘤肠道病毒递送载体的作用，这将把细胞免疫疗法和病毒疗法的效果结合起来。我们针对胶质母细胞瘤细胞系测试了四种非致病性肠道病毒菌株，并评估了产生的感染滴度。接下来，我们探究了这些病毒菌株是否可以通过自然杀伤细胞系NK-92递送至肿瘤，NK-92正作为一种临床上可接受的治疗方法而被积极评估。几种肠道病毒菌株表现出溶瘤特性，但只有柯萨奇病毒A7（CVA7）能在NK-92细胞中高效复制。我们比较了使用NK-92细胞和直接静脉注射时CVA7的递送效率，发现即使单次注射后细胞递送也具有显著优势。这表明NK-92细胞系可被用作递送CVA7溶瘤菌株的载体，这将提高这种病毒溶瘤剂治疗多形性胶质母细胞瘤和其他癌症形式的临床潜力。
