ORIGINAL RESEARCH
Human enteroviruses exhibit selective oncolytic activity in the model of human glioblastoma multiforme xenografts in immunodeficient mice
1 Engelhardt Institute of Molecular Biology, Moscow, Russia
2 Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow
3 Pirogov Russian National Research Medical University, Moscow, Russia
4 N. N. Blokhin Russian Cancer Research Center, Moscow, Russia
Correspondence should be addressed: Peter M. Chumakov
ul. Vavilova, 32, Moscow, 119991; moc.oohay@mpvokamuhc
Funding: the study was supported by the Ministry of Education and Science of the Russian Federation; project code RFMEFI60714X0014.
Stem cells that penetrated deeply into the brain tissue are the main reason behind the relapses of glioblastoma multiforme after surgery. Finding new approaches to counter such relapses, including those that make use of oncolytic viruses, is a pressing issue. This study aimed to determine the sensitivity of cells of human glioblastoma multiforme to non-pathogenic enteroviruses, in vitro and in vivo (mice xenografts model). Glioblastoma tumor cells were exposed to type 1 poliovirus (Sabin vaccine strain), Coxsackie virus A7 (strain LEV8), Coxsackie virus A9 (strain LEV9) and Coxsackie virus B5 (strain LEV14). The virus reproduction intensity and cytolytic activity were assessed through infection of monolayered glioblastoma cell cultures. The ability of glialoblastoma cell cultures (enriched with tumor stem cells) to build subcutaneous tumors in immunodeficient mice after those cultures were exposed to viruses signaled the effectiveness of glioblastoma stem cells destruction. The study revealed that Coxsackie virus A7 and type 1 poliovirus possess the most pronounced oncolytic and replicative properties when tested on gliblastoma cells infected with viruses in vitro and on subcutaneous tumor xenografts in immunodeficient mice (in vivo). Type 1 poliovirus and Coxsackie virus A7 virus prevented development of tumors when glioblastoma neurospheric cell cultures were preincubated with viruses before subcutaneous implantation. Coxsackie virus B5 only managed to reduce the number of tumors developed, and Coxsackie virus A9 did not affect the tumor development at all. Thus, a number of non-pathogenic enteroviruses strains can destroy glioblastoma's stem cells, i.e. they show promise in the context of development of therapeutic agents for relapse-free treatment of glioblastomas.
Ключевые
Keywords: glioblastoma multiforme, oncolytic virus, non-pathogenic enteroviruses, personalized medicine, tumor relapse, experimental cancer therapy