Parvovirus H-1 (H-1PV) exerts oncolytic effects in cell culture models of human brain tumor-initiating cells
Background: Oncolytic virotherapy with H-1PV represents a new therapeutic option for malignant brain tumors currently under clinical investigation in a phase I/IIa H-1PV trial on primary progressive or recurrent glioblastoma. Brain tumor-initiating cells such as glioblastoma „stem-like” cells or medulloblastoma-initiating cells are known to be relatively resistant to conventional anti-neoplastic agents and are thought to give rise to clinical tumor recurrence after standard treatment. This prompted us to address the question whether H-1PV is able to eliminate brain tumor-initiating cells in vitro.
Methods and Results: The expression of stem cell markers was confirmed in neurosphere cultures of glioblastoma „stem-like” cells (n=4) and medulloblastoma cell lines (n=3). Neurosphere cultures were infected with H-1PV at a low (1p. f. u. per cell) or high (50p f. u. per cell) multiplicity of infection. All seven neurosphere cultures underwent productive infection with H-1PV as demonstrated by viral protein expression, viral DNA replication and infectious virus multiplication (increase in H-1PV titers up to 10,000 fold). Virus infection was accompanied by significant cytostatic and cytotoxic effects as quantified by counting living and dead cells, and confirmed by WST-1 assay.
Conclusion: H-1PV is able to infect and lyse brain tumor-initiating cells in vitro without the need to adapt the virus tropism by genetic engineering.