Julie Brahmer was 18 when she first announced, at her high school graduation, that she wanted to cure cancer. Growing up in a small town in Nebraska, she was deeply affected by her grandfather’s five-year struggle with non-Hodgkin lymphoma, a cancer of the lymph system. His suffering sent Brahmer on a career track—medical training at the University of Nebraska, the University of Utah and Johns Hopkins—that, almost three decades later, has put the 46-year-old surprisingly close to reaching her goal.
Brahmer and her Johns Hopkins colleagues are on the cusp of validating a game-changing cancer drug created by Bristol-Myers Squibb. The medication, called nivolumab, is a form of immunotherapy, meaning it improves the ability of the body’s immune system to fend off cancer. Several medical centers and pharmaceutical firms are conducting research along similar lines, but nivolumab is the furthest along. Last December, Science magazine named cancer immunotherapy the breakthrough of the year. According to the magazine, “Immunotherapy marks an entirely different way of treating cancer—by targeting the immune system, not the tumor itself. Oncologists, a grounded-in-reality bunch, say a corner has been turned and we won’t be going back.”
The new drug being tested by Brahmer’s team at Johns Hopkins prevents cancer cells from overriding the immune system. Normally, in the immune system, T-cells hunt down and destroy invaders, such as viruses, and any of the body’s own cells that may be damaged and dangerous, such as cancer cells. But cancer cells have ways of shutting down those T-cells. “With nivolumab, a kind of antibody, we’re targeting one of the pathways the tumor uses to put the brakes on T-cells,” says Brahmer. This kind of therapy is called immune checkpoint blockade. When the drug is successful, tumors melt away—and may stay away even after the medication has been stopped. “For one of my patients, it’s been well over a year since his last treatment, and there’s no evidence of cancer coming back,” Brahmer says.
In phase-one and -two trials, the drug was effective against some kidney cancers and the deadly skin cancer melanoma, but it failed to work in a small number of patients with prostate and colon cancer. Nivolumab has proved especially effective against lung cancer, the deadliest cancer worldwide and Brahmer’s specialty. Many of Brahmer’s lung cancer patients have exhausted other treatments; they had a life expectancy before this trial of under six months. But almost a quarter of those treated with nivolumab at Johns Hopkins have survived two years. The drug is now in phase-three trials, the last step before it can be prescribed to patients.“If all goes well, nivolumab could be available for patients in a year or two,” says Brahmer.
And nivolumab is just the beginning: Brahmer and her colleagues have similar treatments in the works. “We’re developing additional antibodies to block other pathways,” she says. Prominent researchers are excited. “If these drugs really can allow the immune system to effectively attack tumors, it will be a huge leap forward,” says Jean-Claude Zenklusen, PhD, director of the Cancer Genome Atlas Program at the National Cancer Institute.
Brahmer realized early in her medical training that she values dealing directly with sick people. “I always knew I wanted to take care of patients, the way my mom did as a nurse,” she says. And she was drawn to some of the patients with the worst prognoses, those with lung cancer. Brahmer’s mother, in fact, was concerned when she learned her daughter wanted to specialize in lung cancer. “As a hospice nurse, I had seen those patients,” recalls Carol Brahmer. “I asked Julie, ‘Why take on such a tough illness?’ All she said was, ‘Somebody has to do it.’ ”
Doing clinical research—she sees patients but also runs drug trials—allows Brahmer to combine caretaking with science. “In our studies, we take the drugs that have gone through development in a lab and give them to patients in the clinic. At the end of a trial, we send the results back into the lab to figure out why certain patients responded in certain ways,” she explains.