Oncolytic viral therapy is a promising approach to targeted therapy of malignant tumors. In this article we consider the therapeutic potential of a non-pathogenic Coxsackie A7 virus (CA7V) with neurotropic properties on a model of human neuroblastoma. Purpose to study in vitro/in vivo sensitivity of human neuroblastoma HNB (from cell line JMR-32) to Coxsackie virus A7 (CA7V). Objectives: еvaluation of cytolytic activity in vitro on NB cells verified by cytomorphology and assessment of dynamics of the growth of subcutaneous neuroblastoma xenografts in Balb/c nude male mice exposed to CA7V multiple i.v. injections. Material and methods. CA7V was produced in the cells of line-producer С-33А. Cell culture and the strain of transplanted NB (JMR-32) were obtained from the Collection of N.N. Blokhin Russian Cancer Research Center. Cytomorphologic verification of neuroblastoma and CA7V cytolytic activity were executed with the use of standard cultural methods, TCID50 and IC50 criteria. Experiments «in vivo» were performed on immunodeficient Balb/c nude male mice bred and reared in the N.N. Blokhin Russian Cancer Research Center. The experiments were made at day 6 when neuroblastoma subcutaneous xenografts developed to the Vmean = 79-82 mm3 by day 6. The treatment with CA7V at the i.v. single dose of 1×108 cells per mouse was performed 3 times with 72-hours intervals; evaluation of the efficacy was made according to standard criterion Т/С ≤ 42%; and control of the tumor growth rate (Vt/V0) in the dynamics. Statistical assessment was made with the software Excel for Windows 2007 with the use of T-test under p ≤ 0.05. Results. Cytolytic effect of CA7V on neuroblastoma cells was registered similar to basic parameters of the original line-producer С-33А: TCID50 = 0.99×10-4 pfu/cell, and IC50 = 1.11×10-4 pfu/cell; 48 and 72 hours after virus reproduction in NB cells the rate was 2.0 and 1.5-fold higher than in the line-producer cells. СA7V inhibiting effect on the growth of large subcutaneous neuroblstoma xenografts is registered after the first i.v. injection at the minimal level of T/C = 67% (criterion ≤ 42%) with the 1.5-fold decrease of the tumor growth rate and cancellation of early mice death by day 22 vs day 15 in the control group of untreated mice (n = 8). Conclusion. The obtained results allow to consider human neuroblastoma (JMR-32) to possess the low sensitivity to oncolytic effect of in vitro/in vivo. In order to obtain significant effect in vivo the treatment should be started in mice with 2-fold smaller tumors and a higher initial dose of the oncolytic agent.

Effective treatment of malignant brain tumors is still an open problem. Location of tumor in vital areas of the brain significantly limits capasities of surgical treatment. The presence of tumor stem cells resistant to radiation and anticancer drugs in brain tumor complicates use of chemoradiotherapy and causes a high rate of disease recurrence. A technological improvement in bioselection and production of recombinant resulted in creation of viruses with potent oncolytic properties against glial tumors. Recent studies, including clinical trials, showed, that majority of oncolytic viruses are safe. Despite the impressive results of the viral therapy in some patients, the treatment of other patients is not effective; therefore, further improvement of the methods of oncolytic virotherapy is necessary. High genetic heterogeneity of glial tumor cells even within a single tumor determines differences in individual sensitivity of tumor cells to oncolytic viruses. This review analyses the most successful oncolytic virus strains, including those which had reached clinical trials, and discusses the prospects for new approaches to virotherapy of gliomas.