Funding outcome

Viruses such as vaccinia virus have a natural ability to grow in many different types of cells, resulting in cell death. We have modified vaccinia virus so that it is no longer able to infect and grow in normal non-dividing cells, but retains robust replication in tumours. We propose that the anti-tumour activity of this virus could be improved by combining it with a complementary strategy that induces 'programmed' cell death in tumour cells. We have shown that programmed cell death can be activated in a type of ovarian cancer called granulosa cell tumour (GCT) by a protein called TRAIL together with a drug called PAC1 that sensitizes tumour cells to TRAIL. Although TRAIL and PAC1 killed patient-derived GCT cultures in the laboratory, these two agents were not harmful to normal cells. Here we will test whether our modified virus can be used to deliver TRAIL protein to GCT cells, and together with sensitization by PAC1, will be sufficient to eradicate GCT cells cultured in the laboratory, as well as GCT tumours grown in mouse models for this type of ovarian cancer, without harming normal cells. If this treatment is shown to be effective, this strategy could be further developed for the treatment of women with primary or recurrent GCT, and may produce fewer side effects with a more durable anti-tumour response than therapies that are currently available.