A single injection delivering a cancer targeting virus to tumour cells was shown to be effective in a study published in "Nature". According to Jennerex Biotherapeutics, who produced the JX-594 vaccine, the study represents the first trial of an intravenous oncolytic virus successfully expressing transgene products in humans.

Oncolytic viruses are of considerable interest in cancer therapy since they can selectively infect tumours and deliver genes encoding anticancer proteins. While most viruses now in trials are injected directly into tumours it is recognised that what is really needed are therapies that can be injected into the blood stream to seek out metastasized cancer cells.

The JX-594 vaccine is based on the vaccinia virus which has been widely used to vaccinate children against small pox. The vaccine's ability to target tumours is due to the fact that replication depends on Ras proteins which are active n almost all cancer cells.

The virus has been armed with a gene encoding a protein called GM-CSF, which triggers an immune attack against cancer cells. Furthermore a gene for the marker protein beta-galactosidase, has been added, enabling the virus's replication to be tracked.

In the study, led by David Kirn from Jennerex in California , and John Bell from the University of Ottawa, Canada, 23 patients suffering from untreatable metastatic cancers were treated with the viruses. The investigators tried out five doses of the virus and took biopsies of the tumours after eight to 10 days.

Results showed that that seven of the eight patients in the two highest dose groups had evidence that the virus was in place and replicating in their tumours.

Weak staining in nearby healthy tissue showed that the virus had been taken up but could not replicate. Furthermore, six of eight patients in the two highest dose groups experienced a shrinking or stabilisation of their tumours, while those in lower dose groups saw less of this effect. The most common side effects were mild to moderate flu-like symptoms that lasted less than one day.

"Although anti-viral immunity may in theory decrease the efficiency of delivery, all patients on this trial had a history of vaccination with live vaccinia virus as children, and delivery was demonstrated in a patient with neutralizing antibodies present at baseline," wrote the authors.

Reference

CJ Breitbach, J Burke, D Jonker, et al. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature. Doi:10.1038/nature10358