Immune Therapy Against Brain Cancer

Hope, and a chance at something more
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Mar 10, 2008

Eight years ago, 44-year-old Cam Mitchell of Grand Rapids, Michigan was his own boss and in the prime of life. He was happily married and had several nieces and nephews on whom he doted.

He was also four years away from being diagnosed with a deadly brain tumor that usually kills its victims in four to 18 months.

Eight hundred miles away in Durham, Duke cancer researcher John Sampson, M.D., Ph.D., was racing against Mitchell's fate.

Sampson's team was making progress in their effort to create a vaccine that could help the body’s own immune system fight off recurrences of the type of tumor Cam Mitchell was destined to develop. In June 2000 they published a study in Proceedings of the National Academies of Sciences that showed a mouse's immune system could be induced to fight off a brain tumor.

The team had injected into a mouse's brain a specific kind of antibody, a molecule used by the immune system to flag an invader and mark it for destruction. This antibody was developed in the lab specifically to cling to a protein called EGFRvIII on the surface of tumor cells, signaling immune system agents to eradicate the cancerous cells. (See Sidebar: A Sniper at Work)

The results were promising. The highly selective antibody appeared to give the mice long-lasting "immunity" to tumor recurrence.

Could this possibly work in humans?

“I first got involved with immunotherapy research when I came here as a neurosurgery resident,” said Sampson, who is now in his tenth year on the faculty. “I see it as the holy grail of therapy. Chemotherapy, radiation and other man-made treatments can’t make sense of tumor versus non-tumor; they kill rapidly dividing cells indiscriminately."

By contrast, "immunotherapy is all about specificity -- recognizing a tumor cell and killing it, while leaving the healthy cells untouched, like a sniper.”

As a resident at Duke, Sampson quickly found a mentor in Darell Bigner, MD, PhD, a noted researcher and neuro-pathologist who had discovered the EGFRvIII mutation Sampson would later target with his vaccines.

Working in Bigner’s lab, Sampson published a seminal paper on the subject in 1996, showing that a molecule called granulocyte-macrophage colony stimulating factor could boost a mouse’s immune system to the point that it could not only reject subsequently implanted tumor cells, but could also destroy small tumors that were already there.

By 2004, the vaccines that Sampson and his team had been working on for years were ready for their first test in humans.

That was about the time Cam Mitchell suffered a seizure at home one night. Doctors initially thought he had suffered a stroke. But an MRI revealed a mass in his brain, and surgery confirmed that the mass was a glioblastoma multiforme, the most common and most deadly of all brain tumors.

After Mitchell had endured radiation and chemotherapy, his oncologist could only offer a grim prognosis, Mitchell recalls. “I looked at him and said, ‘if this were someone in your family, what would you do?’ He told me about Duke. On my first trip to Durham, they told me about the vaccine program.”

Mitchell started coming to Duke monthly for vaccinations -- nearly four years ago.

He had to sell his business because of the demands of his health care and has had trouble retaining his driver’s license because of seizures likely related to his original tumor or to the radiation treatments. But Mitchell is working part-time, still happily married, and continues to dote on his nieces and nephews.

So far, his tumor has not returned, making his case a remarkable exception, since nearly all glioblastomas recur within eight months.

“Most patients experience no side effects, other than an immune reaction at the injection site,” Sampson said. “This is another great promise of immunotherapy -- the opportunity to treat cancer without toxicity.”

Like Mitchell, 17 other vaccine trial patients travel to Durham from all over the country for their injections, and many of them are also beating the odds.

“When you tell patients about treatment options, you ask them what kind of milestones they are hoping to achieve and you try to help them reach those,” said Denise Lally-Goss, a nurse practitioner who administers the cancer vaccinations. “You’re helping someone get their life back, their independence. It’s an opportunity to give hope to someone who has received a devastating diagnosis: hope, and a chance at something more.”

Lauren Shaftel Williams is a senior media relations specialist in the Duke Medical Center.

Contact

KARL.BATES@DUKE.EDU
(919) 681-8054
@DUKERESEARCH