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Fighter. T cells, like the one shown here, help the immune system kill invaders to the body, such as bacteria.

'Serial Killer' Immune Cells Put Cancer in Remission

By: 
Sarah C. P. Williams
2011-08-10 14:00
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The patient was dying of leukemia. One hundred seventy out of every 200 cells in his bone marrow had a cancer-causing mutation, and his lymph nodes were swelling, a sign the cancer was getting worse. He'd already been on multiple courses of chemotherapy, but his disease showed few signs of improvement. Then, in July 2010, he enrolled in a clinical trial for an experimental treatment, designed to turn his own immune cells against his cancer. Months later, all signs of leukemia had vanished, his physicians report today.

"The surprise was how well this worked in clearing so much tumor so rapidly," says immunologist Bruce Levine of the University of Pennsylvania, one of the scientists who created the new treatment.

The cancer therapy, described today in two papers in Science Translational Medicine and The New England Journal of Medicine, is based on the idea that the human body is already primed to fight abnormal, dangerous cells. T cells, frontline defenders of the immune system, recognize cells that don't belong in the body—such as bacteria—and set off a cascade of events to kill them. Scientists studying cancer have long grappled with how to make these T cells kill tumor cells. But they've never before found the perfect combination of factors to turn T cells into cancer killers.

Levine and his colleagues designed a new gene that can be inserted into T cells to trick them into attacking cancerous B cells, the cause of chronic lymphocytic leukemia (CLL). The new gene encodes a receptor that, on one end, can bind to a molecule that's unique to cancerous B cells. The other end of the receptor sets off a chain reaction when such a B cell is bound, eventually leading the T cell to destroy the cancerous cell. "Essentially, we're converting T cells that would normally recognize other types of cells to be tumor specific," Levine says.

In the initial clinical trial, the researchers tested their method in three patients with CLL. They took a sample of each patient's T cells and added the new gene to the cells, using the same procedure and new gene in each case, while keeping the T cells from each patient separate. Once the T cells contained the new, tumor-specific receptors, the scientists infused the T cells back into the blood of each patient.

All three patients are now in remission. On average, the modified T cells killed over a kilogram of tumor cells in each patient. For every modified T cell infused into the patients' blood, at least 1000 tumor cells were killed, leading the researchers to dub the T cells "serial killers." Moreover, after 12 months, blood tests revealed that the patients still had copies of the modified T cells circulating in their bloodstream able to kill cancer cells. And although the data spans only a year, Levine says the effects are likely even longer.

"The power of these T cells," Levine says, "is that you don't have to keep giving them like you do with chemotherapy drugs. They are a dynamic, living, dividing drug, and you can administer them once and they survive and multiply, continuing to protect against cancer."

The new therapy isn't just a potential boon for CLL patients, says oncologist Walter Urba of Providence Cancer Center in Portland, Oregon. The success of the clinical trial could translate to other cancer types. "You can now try to switch this receptor to recognize a different target," says Urba, who specializes in cancer immunotherapy. "Let's make a breast cancer-specific receptor, and a prostate cancer-specific receptor, and a colon cancer-specific receptor. The potential here is huge to apply this to different tumor types."

And Urba cautions that the current results are based on a small sample size. More work is needed to verify that the treatment is broadly successful in all CLL patients and that stray cancer cells don't eventually mutate so that they avoid displaying the molecule targeted by the T cells.

"This is really exciting," he says. "The results are very promising. But it's also important to remember that this is just a couple of patients and they've only been followed for a short time. We need to see more studies now."

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