Division of Tumor Virology
Prof. Dr. Dr. h. c. Ralf Bartenschlager (in ch.)
Treatment of an intracerebral rat glioma with parvovirus H-1 (H-1PV). MRI of a rat brain bearing a glioma, at the time of infection with H-1PV (left), and 8 days later (right), showing disappearance of the tumor after infection.
© dkfz.de
Our Division is focused on “Anti-Tumor Virology”, the objective being to develop oncolytic viruses (preferentially killing tumor cells) and viral vectors (transferring therapeutic genes into cancer cells). Our activities have led to the launching of the first virotherapy clinical trial in Germany, using the oncolytic parvovirus H-1PV to treat malignant gliomas. Based on virus safety and first signs of anti-tumor activity, a second clinical study of H-1PV in pancreatic cancer patients and several compassionate trials of H-1PV-based combination therapy are currently performed. Four main research & development axes are presently being followed.
1. Basic investigations of the interactions of oncolytic parvoviruses (PV) with host cells are more particularly focused on (i) the molecular pathways involved in PV oncotoxic properties, (ii) the mechanisms by which PV oncolysis triggers antitumor immune responses, (iii) the identification of cellular markers predictive of tumor responsiveness to PV treatment.
2. Preclinical assessment of the anticancer potential of PV includes (i) evaluating the applicability of PV therapy to malignancies in children and adolescents, (ii) developing novel anticancer strategies based on second generation PV (vectors) and combination treatments, (iii) producing recombinant PV for the delivery of cyto- and chemokines into tumors and their microenvironment.
3. A research program accompanying above-mentioned clinical studies of H-1PV in cancer patients has been implemented to analyze both virus and tumor fates after treatment.
4. Our Virus Production & Development Unit standardizes protocols for virus application to humans, and participates in trial-accompanying research.
FUTURE OUTLOOK
Basic research will be pursued to unravel the cellular and parvoviral determinants of permissiveness and killing, respectively. This program is expected to contribute to identifying patients susceptible to oncolytic virus-based treatments (“customized” therapy). Furthermore, our ambition is also to understand and optimize the interplay between parvovirus oncolytic effects and host anti-tumor immune responses. On the translational level, our work aims to broaden the range of indications for a potential H-1PV-based oncolytic virotherapy, and to increase the oncosuppressive capacity of PV through adaptation and engineering. Furthermore, in order to prepare future clinical trials, optimal treatment strategies combining parvoviruses with different classes of antineoplastic and immunomodulating agents will be tested, using various in vitro and in vivo models. Another focus of the Division lies on research accompanying the clinical trials of H-1 parvovirus in cancer patients. Of particular interest is the investigation of viral effects not only on the neoplastic compartment but also on the tumor microenvironment modulating anti-cancer immune responses.
