Published: Jan. 21, 2011
Updated: Jan. 21, 2011
In 2005, David Schmidt was diagnosed with glioblastoma multiforme (GBM), one of the most aggressive of brain tumors.
After surgery, radiation, and chemotherapy, his tumor had not yet recurred, but his doctors told him there was only a 3 to 5 percent chance that things would stay that way.
Today, five years after his symptoms first began, Schmidt is still recurrence-free. He credits that in large part to his enrolling in a clinical trial of a vaccine developed at Duke.
“Enrolling in the trial was one of the few options available. It was either that or just kind of take my chances and hope that the cancer didn’t come back,” Schmidt says. “The vaccine trial was attractive because the side effects were minimal. I’m doing really well.”
This vaccine “trains” immune-system cells to attack EGFRvIII, a protein that is present in 25 to 40 percent of GBMs.
In the phase two trial in which Schmidt was involved, patients whose tumors expressed EGFRvIII and who received the vaccine showed overall improved survival times compared to historical controls -- a median of 26 months, compared to 15.2 months. These patients also experienced a much longer progression-free survival period -- 14.2 months, compared to 6.3 months for those who did not receive the vaccine.
Findings published in the October Journal of Clinical Oncology showed that the vaccine eliminated all of the cancer cells carrying the EGFRvIII marker in all but one of the vaccine group participants, says Duke neurosurgeon John H. Sampson, MD, PhD. The results of that trial and others led to Duke licensing the vaccine to the pharmaceutical company Pfizer.
Sampson and colleagues are now honing a different type of weapon against GBM -- vaccines that aid the immune system’s fight against cytomegalovirus, which is normally latent in the body but that researchers at Duke and elsewhere have discovered is activated in some patients with GBM.
“Because the immune system is especially developed to attack viruses, this provides an unparalleled opportunity for us to exercise immune therapy against these tumors,” Sampson says. Duke is leading single-center phase one and phase two trials of glioblastoma vaccines that target cytomegalovirus.
Duke’s extensive work in developing and testing cancer vaccines means that patients can participate in trials of vaccines for many types of cancers -- brain, breast, colon, ovarian, and prostate.
Duke was an enrolling center for the trial that led to approval of the prostate cancer vaccine Provenge, which in May 2010 became the first cancer vaccine approved by the Food and Drug Administration.
New trials available only at Duke include a study of a vaccine called dHER2 to fight breast cancer that overexpresses the HER2 protein, which is one of the more aggressive forms of the disease. The trial was developed because of findings in mice that Duke oncologist Michael Morse, MD, and colleagues published March 1, 2010, in Clinical Cancer Research.
“We showed that if you use a cancer vaccine in conjunction with a targeted therapy [lapatinib], you get additional efficacy. The vaccine activates T cells and also multiple antibody responses against HER2 that synergize with the HER2 tyrosine kinase inhibitor lapatinib,” Morse says.
If that proves true in humans, the vaccine could improve upon standard treatments for this type of breast cancer, which include chemotherapy plus the monoclonal antibody trastuzumab (Herceptin). “Unlike trastuzumab, which binds to just one part of HER2, the vaccine induces polyclonal antibody responses, targeting different parts of the molecule,” Morse says.
Other work from Duke has also demonstrated the additive effect from combining traditional treatments with vaccines. “We’ve demonstrated in animals and humans that there is a potent synergy between chemotherapy and vaccines; the chemotherapy actually dramatically enhances the effects of the vaccine,” Sampson says.
For now, even after surgery, radiation, chemotherapy, and immunotherapy, recurrences are still all too frequent. But Sampson, Morse, and other Duke investigators work to develop the right combination of treatments that will make survival stories such as Schmidt’s more commonplace.
Learn more about clinical trials at the Duke Cancer Institute.