Infectiology and cancer-therapeutic potential of parvovirusesHead : Prof. Dr. med. Jörg R. Schlehofer

Parvoviruses, including adeno-associated viruses (AAV), are small DNA viruses of various species. They are particularly interesting because of their oncosuppressive properties.RESEARCH PROJECTS:1.Preclinical studies on the oncolytic virotherapy of brain tumors using parvovirus H-1 (H-1PV)

(cooperation with Neurochirurgische Universitätsklinik, Heidelberg [K. Geletneky] and the group of J. Rommelaere; Contract DKFZ/ORYX GmbH)

Malignant brain tumors (notably malignant glioma) are characterized by an extremely bad prognosis despite modern therapeutic efforts including surgery, radiation, and chemotherapy. A very promising alternative therapeutic concept is the use of the oncolytic parvovirus H-1, which does not induce disease in humans and is able to selectively kill malignant cells.

We could demonstrate that in vitro infection with the rodent parvovirus H-1 is cytotoxic for human glioma cell lines and cells established from patients' tumors. The viral cytopathic effect is accompanied by replication of the virus.
In in vivo experiments we achieved complete oncolysis and stable remission of advanced intracerebral rat gliomas (RG-2) by stereotactic intracerebral injection of parvovirus H-1 without any pathologic alteration of brain tissue surrounding the tumor. Similar experiments are under way to demonstrate efficacy of treatment of human glioma xenografts in immunodeficients rats (cooperation with ONCODESIGN, Dijon, and INSERM Tranfert)

Our current project consists of preclinical studies in animal models on the feasibility and safety of using the rat parvovirus H-1 (H-1PV) for the oncolytic treatment of brain tumors.


  • In animal models, routes, dosages etc. of virus inoculation are being established and validated, and replication, expression of viral macromolecules, and biodistribution and shedding of virus are being assessed.

  • Combination of virotherapy with chemo- or radiotherapy is analyzed in vitro and in appropriate animal models.

  • Immunological factors possibly involved in the H-1PV-mediated oncolysis are also investigated, as well as the

  • Sensitivity of glioma stem cells to the oncolytic effect of H-1PV.

  • The protocol for a clinical trial of oncolytic virotherapy on patients with malignant glioma is being established (cooperation with the KKS of the University of Heidelberg).

2. TUMOR SUPPRESSIVE PROPERTIES OF AAV :

(Coop.: Molecular Pathology, Univ. HD [M. von Knebel Doeberitz, S. Dihlmann]; Urology Hospital, Univ. GI [V. Rohde])


  • Improvement of chemotherapy by adjuvant AAV infection: Sensitization of carcinoma cells to chemotherapeutics by AAV (in vitro and in vivo)

  • Identification of cellular factors mediating AAV-induced sensitization of tumor cells to chemotherapeutics and inhibition of adverse side effects of chemotherapy (evaluation of effect in various cancer cells in vivo and in vitro [pancreas, prostate, bladder, colon])

  • Sensitivity of p53+/- cells to cytotoxic effects of AAV

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