Use of Oncolytic Parvoviruses in the treatment of malignant gliomas

Accumulated evidence gathered in the last three decades demonstrated that some members of the Parvoviridae family, belonging in particular to the species Rodent protoparvovirus, have natural antineoplastic activity in cell culture and animal models, and that human tumor cells can be targets for this activity. In an immunocompetent rat glioma model, the H-1 parvovirus (H-1PV) was able to efficiently cure gliomas while raising an antitumor memory immune response. This oncosuppressive effect was observed after virus administration through intratumoral, intravenous and intranasal routes, and appeared to rely on both the direct oncolytic activity of H-1PV, and its handover to the host immune system. The parvovirus was also capable of inducing the regression of human glioma xenografts in immunodeficient rats. These studies have laid the foundations for the launch of a first phase I/IIa clinical trial in which H-1PV is currently undergoing evaluation for its safety and first signs of efficacy in patients with recurrent resectable glioblastoma multiforme progressing in spite of conventional therapies (ParvOryx01 trial). While no clinical conclusions, besides safety, can be drawn at this stage from the trial, there are intriguing laboratory measurements in resected tumors and patients’ blood. Immunohistochemical and FISH analyses provided evidence for virus efficiency in crossing the blood-brain barrier, spreading throughout the tumor and getting expressed in tumor tissues. The possible impact of these direct viral effects on the tumor fate has to be balanced against evidence of immune infiltration and vascular disruption in infected tumors, and of systemic immune responses in treated patients.