Oncolytic Effects of the E Variant of Encephalomyocarditis Virus to Human Neuroblastoma in in Vitro and in Vivo

Abstract

The oncolytic effects of encephalomyocarditis (EMC) virus on of human neuroblastoma (NB) were studied in vitro employing NB cell cultures and in vivo employing tumors grown in nude mice and nude rats. In short-term studies, human NB cell (HTB10) cultures were exposed to the virus 10 4 Tissue Culture Infectious Doses (TCIDs). The TCIDs were used to titer the maximum effect of EMC virus on L-929 cells. In vitro studies showed 100% Cytopathic Effect (CPE) at 48 hours. The CPE was used to observe pathologic effects of the cells. The in vivo studies showed necrosis and degeneration in the tumors grown in nude mice at 7 days following treatment with the virus. The nude mice exhibited a high mortality rate after exposure to the virus. The long-term studies were performed on tumors grown in nude rats, since they were more tolerant to the viral treatment. On the 58th day after the viral treatment of tumor bearing rats, 8 out of the 12 tumors had disappeared, and the remaining 4 tumors were grossly necrotic. The average size of the infected tumors was 2.13 cm 2 as compared with 30.5 cm 2 in the control. Microscopically the treated tumors showed severe necrosis and microcystic degeneration. The observed gross decrease in treated tumor size together with the presented light and electron microscopic studies, support the potential value of viral treatment of neuroblastoma.