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Immunological Patriots

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Immunological Patriots
Nicho Bourque with her daughter.

Nicho Bourque made it a joke at first. She had to. Her dermatologist had biopsied her right middle finger, the one with the ugly mole under her nail, diagnosed her with malignant melanoma and told her she’d have to have the tip amputated. “When you use that finger in high school, that’s what happens: God cuts it off in your adult years,” Bourque, now 38 and a medical technologist in Lake Charles, La., told her coworkers. “Then I realized this could go either way. I could live—or I could die.”

“We’re not waiting,” said her dermatologist, Shondra Smith, who dispatched her to M.D. Anderson Cancer Center in Houston. A couple of weeks after the amputation, in October 2007, the pathology results came back: the cancer had spread deeper. Doctors amputated again, this time to her first joint. Then in an August 2008 followup visit, the doctors at M.D. Anderson delivered worse news: the cancer had moved to her lungs.

Metastatic melanoma is notoriously tough to treat. The best treatments approved by the Food and Drug Administration cause tumor regression in fewer than one patient in five, and patients today have a median survival of less than a year. “They have a very grim prognosis,” says Patrick Hwu, a cancer immunologist at M.D. Anderson. But that could change. To improve the odds for melanoma patients, Hwu has worked for years to boost the ability of immune cells to fight the tumors. A subset of these cells, called T cells, home in quickly and try to destroy the enemy.

But tumor cells release substances that lull these cells into complacency, so Hwu’s team tests auxiliary treatments that awaken them and spur them to fight. In laboratory animals, the researchers had tried vaccinating with fragments from the hosts’ own tumor cells, administering the immune-stimulating protein interleukin-2, tickling receptors on T cells with chemical agents and adding antibodies that in effect take the brakes off the immune system. They had also found that white blood cells called dendritic cells can wake up snoozing T cells and alert them to the danger. It was time to try the treatment in patients. Nicho Bourque was the first.

In a series of visits to M.D. Anderson beginning in November 2008, doctors removed lesions from Bourque’s lungs, cultured the frontline T cells that were trying to fight the tumors and isolated dendritic cells from her blood. In January 2009, in front of a crowd of curious doctors and nurses, they returned both types of cells to her body, then administered interleukin-2 to give the cells a boost. When she returned to the hospital after 12 weeks, her tumors had shrunk 50 percent. Bourque was ecstatic. “I did cartwheels down the hall with my wig on,” she says. It’s not clear whether it was the experimental treatment that caused her cancer to retreat—about 7 percent of patients respond to interleukin-2 alone, and a large randomized trial is needed to find out for sure whether restoring T cells and dendritic cells bolster that treatment, Hwu says. But either way it worked out well for Bourque, who remains in remission a year later. Spontaneous remission is extremely rare for stage IV melanoma, Hwu explains.

By learning how to help T cells fight melanoma, Hwu hopes to develop therapies that also boost immune cells to fight against breast, colon and rectal tumors. “I think we can generalize to other cancers,” he says.

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