'Superglue virus' wipes out brain tumours

时间:2019-02-26 11:13:05166网络整理admin

By Philip Cohen A cold virus with extra-gripping power is an efficient weapon against a deadly form of brain cancer, suggests a new report. These anti-tumour microbes have proved so successful in recent mouse experiments that researchers hope to start a clinical trial next year. The virus, known as Delta-24-RGD, was able to destroy human glioma tumours implanted in mice 60 per cent of the time and unpublished work suggests it can be made even more effective by combining it with other therapies. “We’ve never seen this kind of response before with any other treatment tested in either animals or humans,” says Juan Fueyo of the University of Texas MD Anderson Cancer Center in Houston. Michael Korn, an oncology researcher at the University of California, San Francisco, says: “This work is really nicely done. It definitely warrants bringing the virus into a clinical situation to see what happens.” Glioma is a deadly form of brain cancer that often recurs despite surgery, radiation treatment or chemotherapy. “It is a devastating disease,” says Fueyo. “When you are told you have this tumour, it is a death sentence.” Patients often don’t survive more than one year. So doctors are eager to find new approaches to attack these tumours. One intriguing approach is to give these malignant cells their own disease: a modified virus genetically-engineered so that it only replicates inside cancer cells. Gliomas, for instance, have uncontrolled growth partly because they have a defective retinoblastoma or Rb protein, which regulates chromosome replication. So Fueyo and his colleagues designed an adenovirus that replicates only in the presence of crippled Rb. The virus specifically destroys cancer cells, because normal cells with active Rb easily destroy it. And Fueyo says the strategy worked. The virus did kill cancer cells – when it could get inside. The problem is that an adenovirus needs to grab a receptor protein on a cell’s surface to infect, and many gliomas have few of adenovirus’s preferential hand holds. So the researchers modified the virus again, endowing it with grippers for common proteins on the glioma cell surface called integrins. To test this stickier viral incarnation, three groups of mice were implanted with human tumours and then the tumours were injected with a placebo injection of inactive virus or a salty solution, the original virus, or the new version. Mice treated with dead virus or salt solution died within three weeks. The original virus was able to keep 15 per cent of the mice symptom-free for the 140 days of the experiment. In contrast, 60 per cent of animals treated with the superglue virus survived until the end of the study period, when they were killed and autopsied. These autopsies showed holes and scar tissue where the tumour had been, suggesting it had been completely destroyed. But the scar tissue suggests that layers of healthy cells around the tumour were also destroyed by an unknown mechanism. “It isn’t too surprising,” says Fueyo. “Nature has designed viruses to kill cells, so some toxicity is expected and we need to design strategies to prevent it.” Even so, he points out that current therapy for gliomas is so aggressive, it often destroys a lot more healthy brain tissue. Journal reference: Journal of the National Cancer Institute (vol 95,