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Early in his residency, Sampson knew that mastering complex surgical challenges wouldn't satisfy him over the long haul. Performing delicate brain surgery was one thing, but understanding the pathology of brain tumors—and perhaps unlocking the mystery of what causes them in order to better treat them—was quite another. He took three years out of his residency to work alongside Darell Bigner M.D. '65, Ph.D. '72, an internationally known expert on brain tumors, earning a Ph.D. in tumor immunology and learning how to design and conduct clinical trials.
Since then, Sampson and his colleagues at the brain tumor clinic have helped pioneer the use of immunotherapy—he calls it "the holy grail of therapy"—which uses the body's immune system to fight cancers like GBM. "Chemotherapy and radiation are systemic rather than specific," Sampson says, "so they kill the good cells along with the bad cells. But immunotherapy is very specific. It targets only the tumor cell, and leaves healthy cells untouched."
Through painstaking trial and error, Sampson and fellow researchers developed a vaccine that slowed the reappearance of GBM-specific tumor cells in mice. By 2001, he had received National Institutes of Health funding and approvals to conduct clinical trials in humans. There were no guarantees that it would work; patients who agreed to enter the trials knew that it was risky, unproven. It could be ineffective. It could make the tumor come back even stronger. Or maybe, just maybe, it could buy them more time.
Two days after the craniotomy in Operating Room 4, Cam and Peggy Mitchell fly in to Raleigh-Durham International Airport for their monthly trip to Duke Medical Center. The two have known each other since childhood; her sister sat behind Cam in first grade. Cam was diagnosed in 2004 with a grade IV GBM. His doctor in Grand Rapids, Michigan, gave Mitchell a pamphlet about GBM and told him, "Sorry, there's nothing we can do."
Mitchell's oncologist, though, knew about the research being conducted at Duke. He made a few calls. On a Saturday morning, about a week after his diagnosis, Mitchell's phone rang. It was John Sampson, calling from his home. Mitchell could hear Sampson's two young sons playing in the background. Sampson explained that he was starting to enroll human subjects in an experimental clinical trial.
Was Mitchell interested?
"When you're first given the news that you have a stage-four brain tumor, you really don't expect to survive," says Mitchell. Faced with the prospect of certain rapid decline or the slim hope that he might live a few months longer to see his beloved brood of nieces and nephews pass the next birthday or kindergarten graduation, Mitchell didn't hesitate. "People have told me that they would never want to be a guinea pig, but I don't see it that way. I thought, Hey, I've got to be willing to try something leading-edge. Someone has to be willing, and I'm going to be that person."
In June of 2004, the Mitchells and nearly twenty members of their extended family traveled to Duke to support Cam as he underwent a series of tests to determine whether he qualified for the trial. Trial parameters included, among other factors, how recently the tumor was diagnosed and removed, its size, and whether it contained a specific protein, found on fewer than half of GBMs, that the vaccine was designed to target. When the tests came back confirming that he was a good candidate, "I felt as though I'd been given a lifeline," he says.
Four years later, the Mitchells have come to consider Duke a second home. They've negotiated medical discounts with airlines and hotels, can tell you which food station in the hospital cafeteria makes the healthiest turkey sandwiches, and know that the local Nordstrom can hem a pair of pants in one business day. And they are on a first-name basis with the dozens of physicians, nurses, and support staff members who oversee Cam's health.
On this particular spring trip, Mitchell receives his forty-eighth dose of vaccine. He's brought a CD containing scans of his latest MRI, conducted bimonthly in Grand Rapids, for Sampson to examine for signs that the tumor has started to grow again. Waiting for the results is agonizing. "My mind starts to begin this circle of thought," says Mitchell. "What if I have a recurrence? What if the test is inconclusive? What if the radiologist misses something? Everything related to my treatment is so new that there are no 'norms' to rely on."
Later that afternoon, Mitchell gets the good news that the tumor has not returned. Not this month. Not today. It's a small, temporary reprieve between the exhilaration and dread that have become, in Peggy's words, "the new normal."
Cancer occurs when cells mutate. In some, but not all, GBMs, these mutations take place on the epidermal growth factor receptor (EGFR) of the tumor's surface cells. The mutation, known as EGFRvIII, was discovered by Duke's Darell Bigner and his cancer-research colleagues at the Johns Hopkins University who conduct GBM research. EGFRvIII has also been implicated in a range of other cancers, including breast, ovarian, metastatic prostate, colorectal, and head and neck cancers.
The brain tumor vaccine, which consists of a slightly modified portion of EGFRvIII, triggers the immune system into attacking just those cancer cells. Called CDX-110 and manufactured by AVANT Immunotherapies, the vaccine was developed by Sampson and Amy Heimberger, who completed her internship and residency at Duke. She is now an associate professor at the University of Texas' M.D. Anderson Cancer Center and the lead investigator for a concurrent brain tumor vaccine trial at Texas. "The vaccine works with exquisite specificity," says Sampson. "It's like a silver bullet."
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