Genetically-Modified Virus Explodes Cancer Cells
by Shaoni Bhattacharya
New Scientist
A genetically-modified virus that exploits the selfish behaviour of cancer cells may offer a powerful and selective way of killing tumours.
Deleting a key gene from the virus enabled it to infect and burst cancer cells while leaving normal tissues unharmed, reveals a study by researchers at Cancer Research UK and Queen Mary's School of Medicine and Dentistry, University of London.
Viruses spread by infiltrating the cells of their host. Normally, the detection of an intruder by a cell triggers a process called apoptosis, which causes the cell to commit suicide and prevents the virus spreading further. However, viruses can carry genes that allow them to slip past this cell death process in normal cells, causing infection.
The UK researchers deleted one such gene in an adenovirus. This meant that the virus was immediately detected by normal cells and was unable to spread. But in cancer cells, which grow uncontrollably and ignore the cell death process, the virus was able to thrive and spread rapidly. It then multiplied so vigorously that it killed the cancer cells by making them explode.
"The great thing about this strategy is that the cancer cell does all the hard work," says Nick Lemoine, director of the Cancer Research UK Clinical Centre at Bart's Medical School, who led the team. "It makes more and more virus to infect its neighbouring cancer cells. But if a normal cell is infected, it commits suicide before it can make new virus and spread of the virus is contained."
Unexpected Benefit
The gene the team deleted from the adenovirus is called E1B-19kD. But, as well as removing the cloak the viruses normally use to evade detection by cells, it had another "unexpected" effect, says Lemoine.
This was enabling the viruses to replicate much faster than normal, which in turn helped burst the cancer cells. Previous GM viruses have not shown this effect.
The team examined the effects of the GM virus on pancreatic, lung, ovarian, liver and colorectal cancers in the test tube, as well as on live tumour-bearing mice. The team plans to test the GM virus in clinical trials in people in 2005.
"In tests so far it has proven both potent and selective, although only clinical trials will tell us whether the approach can be an effective treatment in people, "comments Robert Souhami, Cancer Research UK's director of clinical and external affairs.
Lemoine adds that the GM virus could also be armed with additional anti-cancer weapons, in the form of genes producing toxic compounds. "The fact that we have taken a gene out of the viral backbone means we could arm the virus with something that deliberately kills cancer," he told New Scientist.
Journal reference: Molecular Therapy (DOI: 10.1016/j.ymthe.2004.03.017)
by Shaoni Bhattacharya
New Scientist
A genetically-modified virus that exploits the selfish behaviour of cancer cells may offer a powerful and selective way of killing tumours.
Deleting a key gene from the virus enabled it to infect and burst cancer cells while leaving normal tissues unharmed, reveals a study by researchers at Cancer Research UK and Queen Mary's School of Medicine and Dentistry, University of London.
Viruses spread by infiltrating the cells of their host. Normally, the detection of an intruder by a cell triggers a process called apoptosis, which causes the cell to commit suicide and prevents the virus spreading further. However, viruses can carry genes that allow them to slip past this cell death process in normal cells, causing infection.
The UK researchers deleted one such gene in an adenovirus. This meant that the virus was immediately detected by normal cells and was unable to spread. But in cancer cells, which grow uncontrollably and ignore the cell death process, the virus was able to thrive and spread rapidly. It then multiplied so vigorously that it killed the cancer cells by making them explode.
"The great thing about this strategy is that the cancer cell does all the hard work," says Nick Lemoine, director of the Cancer Research UK Clinical Centre at Bart's Medical School, who led the team. "It makes more and more virus to infect its neighbouring cancer cells. But if a normal cell is infected, it commits suicide before it can make new virus and spread of the virus is contained."
Unexpected Benefit
The gene the team deleted from the adenovirus is called E1B-19kD. But, as well as removing the cloak the viruses normally use to evade detection by cells, it had another "unexpected" effect, says Lemoine.
This was enabling the viruses to replicate much faster than normal, which in turn helped burst the cancer cells. Previous GM viruses have not shown this effect.
The team examined the effects of the GM virus on pancreatic, lung, ovarian, liver and colorectal cancers in the test tube, as well as on live tumour-bearing mice. The team plans to test the GM virus in clinical trials in people in 2005.
"In tests so far it has proven both potent and selective, although only clinical trials will tell us whether the approach can be an effective treatment in people, "comments Robert Souhami, Cancer Research UK's director of clinical and external affairs.
Lemoine adds that the GM virus could also be armed with additional anti-cancer weapons, in the form of genes producing toxic compounds. "The fact that we have taken a gene out of the viral backbone means we could arm the virus with something that deliberately kills cancer," he told New Scientist.
Journal reference: Molecular Therapy (DOI: 10.1016/j.ymthe.2004.03.017)
