Improved brain tumour treatment with engineered virus


A new method to treat cancer is to use oncolytic viruses that infect the tumour cells and multiply inside them until they burst. In a recent study from IGP, Di Yu and his co-workers have genetically engineered an oncolytic virus to increase its killing capacity. This is an important step in the development of oncolytic virus for treatment of severe brain tumours.

Oncolytic virus Semliki Forest virus (SFV) has been suggested as a promising candidate for treatment of the severe brain tumour glioblastoma. SFV naturally infects brain cells and causes encephalitis. To use SFV as an oncolytic virus against brain tumours, modified versions of the virus have been produced that only infect brain tumour cells and not healthy brain cells. However, the capacity to kill cancer cells is hampered by the production of an anti-viral substance called interferon, which occurs in virus-infected cells.

In the present study, the IGP researchers aimed to neutralize the interferon response to increase the killing capacity of SFV. To do so they incorporated a gene encoding the protein B18R into the virus genome.

“The idea was that B18R will prevent the induction of the anti-viral response caused by interferon. We studied the effect of the newly engineered SFV-B18R virus on cultured glioblastoma cells and observed an increase in killing capacity and viral spread in the presence of B18R as compared to SFV without B18R,” says Tina Sarén, PhD student at IGP and first author of the study.

Similar results were obtained when the researchers studied the effect of the engineered SFV in a glioblastoma mouse model. After treatment with the SFV-B18R virus tumour growth was reduced compared to tumours in mice that were treated with SFV without B18R.

“Our study supports previous studies that SFV is a good candidate for treatment of glioblastoma and by modifying the virus we bring it one step closer to be used for immunotherapy of glioblastoma,” says Di Yu, who led the study.

The results have been published in the scientific journal Molecular Therapy - Oncolytics

More information:
Article in Molecular Therapy – Oncolytics
Di Yu’s research in Magnus Essand’s group