Immune reprogramming to combat cancer

A technique to reprogramme immune cells to wipe out cancer has been tested successfully by scientists in America.
19 February 2016


A technique to reprogramme immune cells to wipe out cancer has been tested successfully by scientists in America.

One third of the population will ultimately succumb to cancer, but at the moment treatment options remain limited to relatively blunt instruments like radiotherapy and chemotherapy.Stan Riddell

Both of these techniques tend to exploit the fact that cancer cells are growing rapidly and are vulnerable to disruption to their DNA and biochemistry.

Unfortunately, other healthy cells that are also fast growing in the body by necessity, such as those in the intestine, skin and blood, are also vulnerable, leading to sometimes severe side effects.

Now immunologist Stanley Riddell and his colleagues at the Fred Hutchinson Cancer Research Center in Washington State, US, have demonstrated an approach that can turn a patient's own immune system against their cancer.

Of thirty-five patients with a form of blood cancer who underwent the new therapy, more than 90% went into remission.

It involves first removing white blood cells called T lymphocytes from the patients.

In a dish, a virus is used to transfer into the cells a piece of DNA containing instructions for building a structure called a "CAR" or chimaeric antigen receptor.

This is a protein that sits on the surface of the cell and can recognise and lock onto a patient's cancer cells.

At one end of this receptor protein is a tail structure that sticks inside the cell and activates the lymphocyte whenever the receptor binds successfully to a cancer cell.

T cells modified in this way are then injected back into the patient where they circulate in the bloodstream, patrolling for rogue cancer cells to attack. When they find one, the cell activates a death programme and wipes out the offending cancer.

The modified cells also increase in number within the body and persist in the long term, providing an immune memory against the cancer coming back.

The technique is not without risks or complications though. The immune onslaught unleashed by the the T cells as they initially attack cancer cells can lead to significant inflammation in the body, which needs to be controlled to prevent life-threatening complications.

Also, the target that the US team are using to recognise the cancerous blood cells are also present on certain healthy cells, meaning that the treated patients will subsequently lack those cells, which are known as B lymphocytes, forever. These cells normally make antibodies, meaning that the patients will need lifelong transfusions of antibodies to keep them healthy, but this is regarded as a small price to pay for being cured of cancer.

At the moment, the technique has largely been tried against blood cancers because cells floating around in the bloodstream are easier for the modified T cells to seek out and destroy.

In the future it should be possible to develop and optimise the approach to attack solid organ tumours, like lung, liver or bowel cancer too.

"This is the game changer that we've all been waiting for," says Cambridge immunologist Chris Rudd, who is working on developing similar techniques. "Now we know that we can make immune cells recognise cancer cells and we can now activate them so that they will attack and delete tumours."


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