SECTION: Life Science
SCIENTIFIC ORGANIZATION:
Burdenko Neurosurgery Institute, Moscow, Russia.Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences
REPORT FORM:
«Poster report»
AUTHOR(S)
OF THE REPORT:
A.P. Chumakova, A.A. Potapov, S.A. Goryaynov, D.I. Pitskhelauri, G.L. Kobyakov, V.Y. Zhukov, A.V. Poteryakhina, D.V. Kochetkov2, P.M. Chumakov.
SPEAKER:
A.P. Chumakova
REPORT TITLE:
Predicting personalized sensitivity of malignant gliomas to oncolytic enteroviruses
TALKING POINTS:

Malignant gliomas of the brain maintain poor prognosis, with common relapses and development of resistance to radio and chemotherapy. However, cells of malignant glioma commonly acquire increased susceptibility to viruses, because of disorganized tissue architecture, leaky vasculature, suppressed intratumoral immunity and defects in the IFN-system. Nonpathogenic small single-strand RNA enteroviruses are particularly promising for oncolytic biotherapy of brain tumors. However, the success of viral oncolysis might depend on individual properties of patient’s tumor that make malignant cells susceptible to a particular strain of therapeutic viruses. In particular, individual tumors may differentially express some surface proteins that are used as receptors for virus entry. The aim of the study was to develop an approach for prediction of individual sensitivity of gliomas to a set of oncolytic enteroviruses. We selected four non-pathogenic enteroviruses that depend on different host-cell receptors: Poliovirus Type 1 vaccine strain depending on PVR (CD155), Echovirus Type 12, Coxsackevirus B2 and Coxsackevirus B5 depending on CD155 and CAR receptors. We tested the replication capacity of the viruses in three human glioblastoma cell lines U87, U251, A172 and in normal asctrocytes in vitro. Also, we prepared short-term organ cultures of 14 biopsies from patients with low- and high-grade gliomas and tested the ability to replicate the selected enterovirus strains. In parallel, we tested the expression of CD155, CAR and CD155 genes by real-time PCR with RNA isolated from the appropriate cell cultures and biopsies. We found that normal human astrocytes were completely resistant to the viruses. The glioblastoma cell lines and the glioma organ cultures displayed differential sensitivity to the viral strains. We found that the sensitivity of glioma cells to a particular virus correlates with the expression of receptors required for the virus entry into cells. We suggest a rapid RT-PCR test for virus receptors as well as for other determinants of host range could represent a novel personalized approach for choosing the most efficient oncolytic strains for the treatment of gliomas.