Taming a Mutinous Mutant: An Errant Receptor Becomes a Prime Cancer Target

Abstract

Half of the patients were still alive 30 months or more after their diagnosis. On average, patients in the vaccine trial remained tumor free for about 12 months versus about 7 months in patients on either temozolomide regimen. About two-thirds were still alive 2 years after diagnosis, versus 5% of unvaccinated patients with EGFRvIII-positive glioblastomas. While there is reason to be optimistic, the Duke – M. D. Anderson trial was tiny and not randomized so it must be evaluated cautiously. And the glioblastoma vaccine is not a cure. The cancer always recurs because glioblastomas are highly heterogeneous cancers — they comprise many clusters of cells with different features — and the vaccine-primed immune system spares those tumor cells that are devoid of EGFRvIII. Still, in each of nine recurrent tumors examined for its presence, none of the mutant protein remained, Heimberger says, suggesting the vaccine is performing as designed. But why does this one work when so many previous attempts have failed? First, these were newly diagnosed patients, in better shape than patients who have failed prior therapies, Heimberger says. Second, only residual traces of the tumor remained after surgery, disabling the myriad decoys and traps solid tumors evolve to defl ect immune responses. Finally, EGFRvIII is an ideal immuno