Engineered virus thwarts ovarian cancer in mice

2019-03-02 07:05:00

By Roxanne Khamsi Doctors could soon have a new weapon for fighting one of the toughest malignancies – ovarian cancer. Tests conducted in mice show that a virus engineered to target cancer cells and kill them can completely suppress these tumours if it is given quickly enough. The authors hope to begin human clinical trials of the therapy within two years. Scientists began exploring the idea of using specially modified viruses to fight ovarian cancer in the early 1990s, trying modified adenoviruses and herpes viruses. These were “safe but not effective” in treating the disease because they were not aggressive enough, explains David Bartlett of the University of Pittsburgh School of Medicine in Pennsylvania, US. His team instead focused its efforts on the vaccinia virus group, which has previously been used to vaccinate people against smallpox and is generally safe to humans. These viruses are more potent than adenoviruses and herpes viruses because they carry an enzyme called DNA polymerase to kick-start viral replication within cells. Bartlett’s team created a modified vaccinia virus that would target and kill cancer cells. They did this by removing genes in the virus that help it to produce a growth protein. This means that the virus survives best in cancer cells that can supply it with large quantities of this growth protein, as opposed to non-cancerous cells that only produce very small amounts. The vaccinia virus was also engineered to carry a gene for an enzyme called cytosine deaminase that causes cell suicide in the cells it infects. The researchers injected mice with ovarian cancer cells and then either gave them an immediate injection of the engineered vaccinia virus, or waited 30 or 60 days before infecting them with the virus. A fourth group of mice injected with cancer cells were not given any treatment. Of the mice given the immediate injection, 90% were still alive 180 days later and showed no signs of tumour growth, says Bartlett. Some 10% of the mice given the virus 30 days after being injected with ovarian cancer cells survived to that point as well. The mice that received vaccinia virus injections 60 days after exposure to the cells lived on average to 125 days – around 50% longer than their control counterparts – though all mice in these groups were eventually killed by the cancer. The findings were presented on Saturday at the annual meeting of the American Society of Gene Therapy in Baltimore, Maryland, US. This year, more than 20,000 US women are expected to be diagnosed with ovarian cancer and 15,000 will die from the illness, according to figures from the American Cancer Society. Bartlett hopes that his treatment could one day be adopted to treat women, particularly to obliterate ovarian cancer cells that linger after surgery. Ovarian cancer is a “particularly good target” for this kind of therapy, according to David Curiel of the University of Alabama at Birmingham, who plans to start human clinical trials using adenoviruses to treat the illness in the autumn. He explains that at a certain stage of the disease the tumour cells may spread within the peritoneum, a membrane that forms the lining of the abdominal cavity. Because the peritoneum is a confined space, the therapeutic viruses can be delivered and concentrated within that area. Curiel says Bartlett’s approach is also promising because it involves “arming” the virus with a gene to kill cancer cells. However,