Stephanie Lipscomb was 20 years old when she was diagnosed with Stage IV glioblastoma—a tumor in her brain the size of a tennis ball.The nursing student thought that she had months to live. She entered a clinical trial at Duke in 2012 that provided a seemingly miraculous recovery. Nearly five years later, she remains cancer-free.Lipscomb’s story was covered extensively in a recent 60 Minutes special on breakthrough cancer research at Duke. The research that led to her treatment, however, has been decades in the making. For most cancer patients, treatment options have traditionally centered around the so-called “three pillars”—surgery, radiation therapy and chemotherapy—explained Smita Nair, an associate professor of surgery and pathology and the leader of Duke’s Tumor Microenvironment/Immunotherapy Focus Group.In the past several years, however, researchers at Duke and across the globe have made significant advances in re-purposing the body’s natural immune defenses, using these modifications to directly attack cancer. This approach, called immunotherapy, has been decades in the making, Nair said, noting that countless setbacks have preceded major breakthroughs in the field. In one well-publicized example, scientists at Duke’s Preston Robert Tisch Brain Tumor Center engineered a modified version of the poliovirus that could be used to treat brain tumors in some patients who had exhausted all other options. The poliovirus was developed and refined through decades of work by Dr. Matthias Gromeier, a professor of neurosurgery, explained Dr. Peter Fecci, the leader of Duke’s Brain Tumor Immunotherapy Program.Fecci added that the design of the modified poliovirus lets it latch on to tumors, where it then attracts the body’s immune cells to target the virus and attack the tumors at the same time.In 2012, Duke began its first clinical trial for the treatment, enrolling 65 patients with glioblastoma, a notoriously aggressive brain tumor. Twenty percent of the patients survived for more than three years, compared to the historical four percent survival rate. In May, the poliovirus therapy was awarded “breakthrough” status by the Food and Drug Administration, and the Brain Tumor Center’s findings were showcased shortly thereafter in a 60 Minutes special. “In the aftermath of the special, the phone was off the hook here with people wanting access to trials, even people with tumors that none of these trials were even appropriate for,” Fecci said. “We can’t treat everyone unfortunately, but we would love to have every patient come to Duke.” Humble beginningsDuke’s success was not the first major breakthrough in immunotherapy, however, with many tracing its clinical roots to researcher James Allison and his development of a class of drugs called checkpoint inhibitors. By blocking checkpoints which normally act as “brakes” to keep immune cells from attacking cancer, these drugs can actually activate the immune response. Allison developed the first checkpoint inhibitor, called ipilimumab, which was approved by the FDA in 2011 for treating aggressive melanoma.Ipilimumab’s groundbreaking success marked the beginning of an explosion in immunotherapy treatments, bringing more funding and public attention to the field.