Combined infection with oncolytic viruses (OVs) induces synergistic and additive cell death in glioblastoma multiforme (GBM) cell lines

Experiments documented the use of OVs as a promising therapy of targeting only GBM tumor cells. Studies revealed that a combination of pathways is necessary to profit the most of immunogenic reactions. We analyzed the form of cell death after single and simultaneously administered OVs infection performing MTT, flow cytometry, Immunofluorescence, and Caspase-Glo 3/7-Assay in U87 and U373. We could prove that a combined infection of Reovirus (RV) with Parvovirus H-1 (PV) has a synergistic cell-killing effect with higher rates in apoptosis, necroptosis, and necrosis than an infection with one of these OVs alone, always applied in equivalent MOI. RV plus Newcastle Disease Virus (NDV) coinfection shows additive tumor cell killing effects only in necrosis and necroptosis. Apoptosis remains equivalent to a single NDV infection. PV plus NDV coinfection is less apoptotic despite more cell death, thus resulting in a shift towards necroptosis and necrosis related cell death. Our data indicate that a synergistic anti-tumor effect can be achieved by targeting different cell death mechanisms through combined infection with OVs in two different GBM tumor cell lines.

Publication History

Article published online:
13 May 2020