Gene therapy of human brain tumors
Project management at the University of Würzburg:
A suicide gene transducing retroviral vector system was established, which is based on a replication-competent foamy virus vector. Three different suicide gene ? prodrug combinations (Polynucleosidephosphorylase [PNP] - 6-Methylpurindesoxyriboside [6MPDR]; Nitroreductase [NTR] ? 5-Aziridine-1,2,4-Dinitrobezamide [CB1954]; Thymidinekinase [TK] ? Ganciclovir [GCV]) were tested in a mouse xenograft tumor model. To this purpose human U87 and G59 glioma cells were subcuntaneously injected into nude mice. Four groups of mice were compared: (i) mice received tumor cells only; (ii) mice received tumor cells plus prodrug; (iii) mice received tumor cells plus suicide gene-transducing vector virus plus prodrug; (iv) mice received tumor cells plus vector virus. Compared to the control mice in groups (i) and (ii) 33% (PNP + 6MPDR), 62.5% (NTR + CB1954) und 25% (TK + GCV) of the mice in group (iii) survived. Surprisingly of group (iv) also 66% (PNP), 75% (NTR) und 37.5% (TK) of the animals surivived. This suggests a direct oncolytic effect of replicating foamy virus that was corroborated by infecting tumors with wild-type foamy virus. 37.5% of animals in this group survived.
Projekt period: from 07.1998 to 08.2001