*4.8. Oncolytic Parvovirus H-1*

Oncolytic parvovirus H-1 is a single-stranded DNA rodent protoparvovirus 1 virus [18]. The lack of pre-existing immunity in humans makes parvovirus an interesting oncolytic virus to explore in the clinic [151]. Oncolytic H-1 parvovirus was administered intratumorally and intravenously in recurrent GBM patients in a phase I/IIa trial [152]. Robust immune response in terms of high infiltration of cytotoxic T cells was observed in the

oncolytic parvovirus patients in this first study. Furthermore, in peripheral blood of the patients, specific T cell responses against glioma and viral antigens were detected [152]. Unlike for many other oncolytic viruses, antiviral type I interferon responses are not evoked by parvovirus infection [152]. Interestingly, parvovirus infection of GBM cells is followed by cathepsin B upregulation [152]. Inhibition of cathepsin B protects the glioma cells from parvovirus oncolysis, highlighting cathepsin B's importance in the parvovirus infection [153].
