Oncolytic Viruses

Oncolytic viruses selectively replicate in tumor cells without affecting healthy tissue. The selectivity of oncolytic viruses for transformed cells might be due to interactions of their non-structural proteins with host cell factors involved in cell division which are often overexpressed in tumor cells, thus providing a significant difference in comparision to healthy cells. Due to their selectivity for tumor cells oncolytic viruses represent a promising and attractive field of research for the development of novel compounds for the treatment of diverse tumor diseases.
In case of the glioblastoma, which is the most frequent human brain tumor disease, it was shown that rats carrying an implanted brain tumor could be completely cured by infection with oncolytic parvovirus H-1 without affecting any healthy cells. Due to this success in rats, a clicical trial with glioblastom relapse patients has been started of which the success still has to be validated.
The exact mechanisms accounting for parvovirus H-1 and other oncolytic virus selectivity has not been completely understood so far. However, several studies revealed that the viral non-structural protein NS1 is the main effector of parvovirus cytotoxicity by interaction with host cell factors like casein kinase II and tropomyosin, mediating the death of the infected tumor cells. Furthermore, NS1 is highly phosphorylated by the host cell which also contributes to the cytopathic effect. However, the precise function and role of the NS1 within the oncolytic process is still to be elucidated.
Focus of this project is the structural-functional analysis of selected non-structural proteins from oncolytic viruses. The aim is the analysis of homologies and differences between different virus strains as well as by identification of putative interaction partners from tumoral host cells. Data of structure and dynamics of oncolytic virus non-structural proteins will give new evidence for their mechanism responsible for the selective cytopythic effect and thus providing a novel approach for the development of drugs used in treatment of tumor patients.

Contact person for this project: Marco Klinge