Brain Tumor Vaccine Developed By Stanford Researcher To Be Tested At 20 Sites Nationally (5/24/2007)

An experimental vaccine developed by a researcher at the Stanford University School of Medicine to treat a rapidly fatal brain tumor called glioblastoma will be tested in 20 U.S. sites including Stanford.

For Albert Wong, MD, professor of neurosurgery and member of the Stanford Comprehensive Cancer Center, 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.

Early test results of the vaccine have spurred researchers to conduct a 20-center trial sponsored by Celldex, a New Jersey company that makes the vaccine. Wong has stock in Celldex and is a consultant to the company.

Stanford is one of the 20 sites in the new phase-2 study, coordinated by researchers at M.D. Anderson Cancer Center and Duke University, which will include 90 patients nationwide.

The vaccine arose from a 1992 discovery made by Wong and colleagues while he was a postdoctoral fellow at Johns Hopkins University in the lab of Bert Vogelstein, MD. 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.

Wong developed the experimental vaccine while on the faculty at Thomas Jefferson University. In later work, he 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. Many of the patients had their tumors shrink, but not enough time has yet elapsed to know whether it prolonged their lives.

Researchers 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 average survival rate.

In a follow-up phase-2 trial of 23 patients in which Duke researchers partnered with colleagues at M.D. Anderson, the average survival increased 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. Researchers plan to publish results from both trials in the next year.

Like the previous phase-2 trial, the new study will only enroll patients whose tumors produce the altered protein.

Note: This story has been adapted from a news release issued by Stanford University

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