Stanford brain tumor vaccine to be tested nationally

When Susan Wright learned that she had a type of fatal, rapidly growing brain cancer at age 46, her doctors at the University of Florida told her she wouldn't live more than 18 months.

Three years later, Wright is still alive, rides her bike and spends days canoeing on a local river. "I can't do things at the level that I used to, but I'm still here," she said.

Wright and her doctors attribute her survival in part to a new vaccine, developed by a researcher at the Stanford University School of Medicine, to treat her aggressive brain tumor called glioblastoma. Although her doctors in Florida didn't have access to the vaccine, they sent Wright to Duke University where she spent the next year receiving the experimental treatment in a clinical trial.

"I remember that as a time of great health and optimism," she said. However, Wright has not been cured, and has since had a relapse and is on chemotherapy. But even with the relapse, the vaccine has helped Wright lived longer than most glioblastoma patients, who have an average survival rate of less than a year.

Now the vaccine will be tested at Stanford as well as other sites nationwide. Originally developed by Albert Wong, MD, professor of neurosurgery and member of the Stanford Comprehensive Cancer Center, results so far have been promising enough to spur a 20-center trial sponsored by Celldex, the New Jersey-based company developing the therapy. Wong has stock in Celldex and is a consultant for the company.

The vaccine is already attracting interest, and is scheduled to be featured during the March 22 "CBS Evening News" broadcast in a report by anchor Katie Couric.

Stanford expects to begin enrolling patients in the trial in April. For Wong, the start of this trial is the result of a career-long interest in the vaccine and in curing glioblastoma. "When you hear about people being diagnosed with brain cancer and dying several months later, that's usually glioblastoma," he said. Any treatment that improves survival time in people with the disease is a significant improvement, he said.

Only 3 percent of people with glioblastoma survive five years, with the average survival being just under a year. The disease resists treatment with chemotherapy and radiation, and spreads so effectively throughout the brain that a surgeon can no more remove every last cell than a picky eater could remove every bit of cheese from a casserole.

The vaccine arose from a 1992 discovery Wong made while he was a postdoctoral fellow at Johns Hopkins University. He found that in many glioblastomas the cells are dotted with an unusual form of a common protein called epidermal growth factor receptor, or EGFR. Although the gene for that altered protein doesn't contain any mutations, the cells inexplicably chop out several chunks of the normal protein before lodging it on their cell surface. He named this unusual variant EGFRvIII because it was the third variant he had discovered.

Anything that makes a tumor cell look different from the surrounding tissue intrigues researchers hoping to develop cures. In this case, Wong thought he could direct the immune system to attack cells carrying EGFRvIII by administering a vaccine. The activated immune cells resulting from the vaccine would ignore normal versions of EGFR on other noncancerous cells throughout the body, attacking only the cancer.

In later work, Wong realized that other solid tumors - such as those in the lung, prostate and ovary - also sport EGFRvIII. This made him think that a vaccine that attacks the unusual protein might be widely useful in treating these tumors.

In mice, the vaccine worked exactly as Wong had hoped. Based on that success, colleagues at the University of Washington started a small phase-1 trial to test the vaccine in patients with ovarian and prostate cancers that contain EGFRvIII. Each of those patients showed a response to the vaccine, but so far not enough time has elapsed to know whether it prolonged their lives.

Wong's colleagues at Duke University started another small phase-1 trial, this time testing the vaccine in people with glioblastoma. In that trial, 14 patients who got the vaccine lived on average more than 21 months. That's still not considered a cure, but it's a significant improvement over the typical survival rate.

In a follow-up phase-2 trial of 23 patients in which Duke researchers partnered with colleagues at M.D. Anderson Cancer Center, the average survival went up to about 30 months because of some changes in how the doctors delivered the vaccine and in the types of patients selected to receive it. The previous trial had accepted all glioblastoma patients, whereas this one only accepted patients whose tumors made EGFRvIII. That was the trial in which Wright participated. Results from both trials will be published in the next year.

The phase-2 trial opening up at Stanford will include 81 patients-the largest trial of the vaccine to date. Like the previous phase-2 trial, this one will only enroll patients whose tumors produce the altered protein.

For her part, Wright hopes those people experience the same tumor response and good health she felt while on the vaccine. "It's the only treatment I've had where I felt no side effects," Wright said. "It was really a wonderful experience."

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