Researchers unleash natural killer cells against disease

Montreal team found manipulating cells eliminated cancer quicker in mice

A group of Montreal scientists has found a promising new way to boost the immune system to fight cancer and infectious diseases such as hepatitis.

Coursing through the bloodstream of every human are infection-fighting white blood cells. There are about a dozen different types of white blood cells, including one called the natural killer.

Natural killer cells squeeze their way through the walls of blood vessels into human tissue to search and destroy other cells that are either abnormal, cancerous or infected with viruses. Without those cells, people would suffer many more infections.

Scientists at the Institut de recherches cliniques de Montreal have discovered a key protein in the natural killer cell that could be manipulated for the purposes of cancer therapy. The protein, called EAT-2, acts as a kind of brake, reigning in the killing ability of natural killer cells.

Without EAT-2, natural killer cells would "overdo" their job, explained Andre Veillette, director of molecular oncology research at the institute.

This would be a bad thing in a healthy person. But what about someone who has metastatic cancer or is infected with the hepatitis C virus? If their natural killer cells could be manipulated in such a way as to release the EAT-2 break, it's possible their cancer or infection could be cured, say the researchers.

To test their hypothesis, the scientists injected rat tumour cells in the bellies of a dozen lab mice. The scientists had already "knocked out" the EAT-2 protein in the natural killer cells of half the mice through genetic engineering.

In the control group, the natural killer cells were left untouched. The researchers found a striking difference.

In those mice whose natural killer cells were modified, the tumour cells were killed very quickly -- in well under two hours. In the control group, half of the tumour cells were destroyed after two hours.

Thus, in the control group the normal natural killer cells did their job, but not nearly as efficiently as in the mice with the "super" natural killer cells, Veillette said.

"The idea would be if you could remove the EAT-2 protein with (drug) inhibitors or blockers, or destroy this molecule somehow in humans, perhaps you could enhance the function of the natural killer cells to fight cancer cells," he said.

The research findings were released Monday in the journal Nature Immunology.

Veillette suggested a cancer patient's natural killer cells could be extracted from the blood and manipulated in the lab to boost their search-and-destroy capability. The modified, "super" natural killer cells would then be injected back into the patient.

The problem with most cancers is that there are micro-metastases -- undetected malignant cells that have spread to other parts of the body. Super natural killer cells might have the power to track them down and kill them before they can do more harm.

Veillette cautioned, however, that such a treatment would probably have to be undertaken in combination with chemotherapy. What's more, it would probably take years for a drug company to develop a treatment.

It is also conceivable this form of immunotherapy could be used to fight infections like hepatitis, Veillette said.

Montreal Gazette