Friday, March 5, 2010

Vaccine may shift odds against deadly brain cancer

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Durham, North Carolina (CNN) -- The first week of each month, Karen and Jerry Vaneman pack their car for a four-hour drive from Asheville, North Carolina, to the medical complex at Duke University. Inside the Preston Robert Tisch Brain Tumor Center, Karen waits patiently as a parade of doctors and technicians pokes and prods, taking samples of all kinds. On this day alone, she gives 21 vials of blood.
In March 2008, Karen was working out in the gym at UNC-Asheville when her left arm went limp. She felt so faint and dizzy that she had to sit. When the Vanemans first got to the emergency room, the doctors were afraid that Karen was suffering a stroke or heart attack.
In fact, Vaneman, a retired professor of Shakespeare and medieval literature, had brain cancer: a glioblastoma or GBM, the most common type of brain tumor. Many doctors consider it a death sentence, but not the team at the Preston Robert Tisch center, where Vaneman was directed for surgery and post-operative care.
"Other doctors will tell you you've got six to nine months, maybe a year to live," says Dr. Henry Friedman, the center's director. "'You're incurable; move on with your life the best you can.' But it's a self-fulfilling prophecy."
At Duke, aggressive treatment is the rule. Almost every patient is enrolled in a clinical trial. For Vaneman, that meant a novel vaccine.
The vaccine, based on research done at Duke and Johns Hopkins, and produced by Pfizer, is called CDX-110. It's not a vaccine in the traditional sense: It doesn't prevent disease. But like any vaccine, it triggers the immune system to attack an intruder, in this case, the cancerous cells.
"All the cells in our body have a [genetic] fingerprint," said Dr. John Sampson, a surgeon and researcher who helped develop the vaccine. "The immune system can recognize differences in those fingerprints."
CDX-110 targets a particular protein -- one with the unwieldy name of EGFRviii, or "EGFR factor three." There is a huge amount of genetic variation within even one patient's tumor, which is one reason the disease is so hard to treat. But according to Sampson, about 40 percent of tumor cells produce EGFRviii. It acts like a homing beacon for the disease-fighting immune cells that are stirred up by the vaccine.
"We're using white blood cells called T-cells, antibodies, to attack the tumor cells because [the tumor cells] have a different fingerprint from the normal cells in the body," Sampson says.
"Unlike chemotherapy, which really hurts all dividing cells in the body, or radiation... the immune system can be absolutely precise. And so we get a very tumor-specific attack with very low toxicity," he says. That means patients suffer fewer side effects.
A vaccine approach is not unique to brain cancer; several are under investigation. Last summer, researchers presented data showing that another vaccine could extend survival for prostate cancer patients.
CDX-110 is not the only candidate for a brain cancer vaccine, either. A project at the University of California, San Francisco, takes a more radically personalized approach. The vaccine for each GBM patient is custom-made from that patient's own tumor cells. Each drug is one-of-a-kind.
"This is the ultimate personalized medicine," says Dr. Andrew Parsa, the neurosurgeon who is running the trial. "It's like having a lot of little medicines instead of one big blockbuster."
The vaccine works -- he hopes -- by targeting something called a heat-shock protein, which is produced in high quantity by tumor cells.
Another novel aspect of the UCSF research is that it doesn't involve a pharmaceutical company as a backer. Instead, it's funded completely by the National Cancer Institute and a handful of cancer nonprofits.
One of the funders, Deneen Hesser, research director of the American Brain Tumor Association, says the research on vaccines is exciting and about expanding the realm of possibility.
"Vaccines represent treatment options," Hesser says. "For patients to be able to have choices, choices in how to approach a treatment plan, is really much different from historical approaches to treating brain tumors."
The UCSF trial is still in its early stages. The current Phase 2 trials -- testing whether the vaccine is effective -- have been enrolling patients only since last summer. The research with CDX-110 is further along, but results from the first multicenter trial will not be made public until later this spring. Forty-four hospitals and medical centers are participating.
At least one of Sampson's patients has made it six years without his tumor coming back. Still unclear is just how many other patients can benefit. Parsa, at UCSF, says his hospital tested 14 patients for the multicenter study. Only one had a tumor that was vulnerable to the vaccine.
In Asheville, Karen Vaneman calls herself lucky.
"In the last year, I've been more mindful of my priorities," Vaneman says. "My family, and the granddaughter, and my husband who has been like a rock through the whole thing. And beyond that, trying to keep a connection with the rest of life, too -- the birds, the bees, the rocks, things like that."
She's hiking again through the hills around Asheville, although she limits the walks to about 2 miles these days. She feels good. And she's happy, more than happy, to put up with the monthly trips to Durham.
"As long as the vaccine works, I'll be getting the monthly shots. And when it doesn't work [any more], then I'm in trouble."

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