The fight against cancer goes viral

TOKYO — Anyone who has suffered through a lingering cold has firsthand experience that viruses are resilient, annoying pathogens. But our opinion of viruses might improve a great deal if they could be trained to fight cancer.

Researchers at Tottori University and the University of Tokyo's Institute of Medical Science are doing just that. So far, the results are promising. They have confirmed the safety and effectiveness of genetically engineered smallpox and measles viruses in attacking cancerous tumors in animal trials. The bugs are altered to keep them from infecting healthy cells, then injected into the bloodstream to do their work.

Researchers at both institutions believe the method could lead to new cancer therapies to supplement surgery, chemotherapy and radiation. But first, they must confirm the effectiveness and safety of the new method in humans.

Cancerous tumors grow by creating blood vessels that feed them. When a therapeutic virus is injected into the bloodstream, it circulates through the body until it reaches the tumor. It then infects the cancer cells. The virus kills the cancer cells as it spreads through the tumor, causing it to shrink or disappear. The viruses can also be used to stimulate the immune system to attack the cancer cells.

Targeting cancer

A research team led by Takafumi Nakamura, an associate professor at Tottori University, has come up with a way to target malignant cells in lung and pancreatic cancers using the vaccinia virus, which is used in smallpox vaccines. The team genetically altered the virus so that it multiplies in cancer cells but is harmless to healthy ones.

The researchers injected human pancreatic cancer cells into the abdomens of mice, causing tumors to grow in them, then injected the mice with the virus. They found that more than 90% of the cancer cells had died. "The virus was originally used in vaccinations, so it is very safe," Nakamura said. His team hopes to confirm the safety of the virus in animals closer to humans, including monkeys, and start clinical trials in five years.

Professor Chieko Kai and her team at the University of Tokyo's Institute of Medical Science have developed a method that uses a measles virus to treat breast cancer. The researchers found that the virus infects breast cancer cells by sticking to a protein, PVRL4, on the surface of the cell. As with the Tottori University trial, they genetically altered the virus so that it multiplies only in breast cancer cells.

When the virus was injected into mice implanted with cancerous tissue, the cancer grew little and most cells in the tumors died. When the virus was administered to healthy monkeys and dogs, it had no apparent side effects or safety problems. "The likelihood of the virus infecting noncancerous cells is low," Kai said. She wants to start clinical trials as early as 2016.

Treatment without trauma

Viral therapies are likely to be easier on patients than surgery and chemotherapy. And as the virus moves through the bloodstream, it can attack small malignancies that escape the surgeon's knife, as well as metastatic cancers.

This approach, while promising, is not without drawbacks. The patient's own immune system may kill the viruses before they reach their target. The more they are used, the stronger the body's immune response is likely to be. Devising effective treatments therefore means coming up with bugs that can evade the body's natural defenses.

There are also concerns therapeutic viruses may mutate in the body and attack healthy cells. The safety and efficacy of injected viruses have so far been confirmed only in animal experiments. And the long-term effects of these viruses on humans have yet to be studied. Researchers will have to find ways of dealing with potential side effects.

Tomoki Todo, a professor at the Institute of Medical Science and a leader in the field, started a clinical trial in late December for a brain tumor treatment that uses a genetically modified herpes virus. So far, there have been few side effects and therapeutic effects have been confirmed, Todo said.

Viral therapies offer new ways of fighting disease, but work remains before viral weapons can be deployed in the battle against cancer.

(Nikkei)

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