A "Sniper" at Work

Singling out cancer cells for attack
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Mar 10, 2008

Scientists have been looking for a way to use vaccines to enlist the body’s immune system in fighting off cancer for nearly a century. The theory is that malignant cells must exhibit mutations or changes in gene expression that the body could recognize as foreign and try to fight them off, in much the same way it identifies and attacks a virus.

In practice, the immune system needs a little help figuring out who the bad guys are.

The vaccine Duke's John Sampson uses is a specialized protein called an antibody that adheres to a receptor called EGFRvIII on the surface of cancer cells. This receptor can be overabundant and mutated in tumor cells. The antibody attaches to the receptor, where it serves as a signal to patrolling immune system cells, telling them that this is a cancer cell that should be destroyed.

Finding the EGFRvIII target was somewhat serendipitous, Sampson said. “In our first trial, we didn’t require the patients to express the protein in their tumors, we injected all comers. But we found that the patients who did well had tumors that did express EGFRvIII and those who did poorly did not.”

To ensure the difference was real and not just chance, Sampson made expression of the protein a prerequisite to admission for the second and third waves of the trial, and confirmed his speculation that EGFRvIII was the key to the vaccine's success. About half of glioblastoma multiforme patients express this protein on their tumors. Cam Mitchell (see related story) had “gobs” of this protein on his tumor, Sampson said.

Brain tumor vaccine patients at Duke receive monthly injections in the groin, where lymph nodes are plentiful and medicine uptake is thought to be ideal. From there, the antibodies boost immune function and, Sampson hopes, help patients’ own immune systems stave off any trace of tumor cells that might be fighting their way back after treatment.

Sampson developed the vaccine in his lab at Duke, and it was licensed in 2006 by a drug company called Celldex Therapeutics, which recently merged with Avant Immunotherapeutics. If the current Phase III trial is successful, the company will likely apply for FDA approval to market the vaccine.

Lauren Shaftel Williams is senior media relations specialist in the DukeMedicalCenter.

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