Doctors and scientists have discussed the idea of immunotherapy for more than a century. The concept seems simple: The body's immune system provides natural defenses against cancer, so why not strengthen these defenses by causing natural brakes on the immune system to fail, or by triggering immune response accelerators? But only in the past two years has understanding of the immune system advanced far enough to produce ipilimumab and the controversial prostate cancer vaccine, Provenge, approved in 2010.
Ipilimumab blocks a molecule called CTLA-4 from doing its usual job: dampening down the activity of the immune system's "killer" T cells that normally attack diseased cells and foreign invaders. Provenge is made by infusing a patient's own immune cells with a combination of two proteins that stimulate the cells to attack prostate cancer cells. Neither of these drugs is a miracle cure: Questions have been raised about whether Provenge really does any measurable good, and ipilimumab only helps a small fraction of patients—around 10 percent. Still, in the clinical trial that led to approval of ipilimumab, more than half of the melanoma patients who responded to the drug survived for more than two years after taking it, and 20.8 percent survived for at least three years, compared to 12.2 percent of those who received the usual chemotherapy alone.
In 2009, researchers testing a new immunotherapy in kids with neuroblastoma stopped the trial early when it became clear that only 34 percent of children who received it saw their cancers return within two years, compared to 54 percent of those who didn't. The treatment targets a molecule called GD2 that is expressed by cancer cells, alerting the immune system to their whereabouts. In June, researchers announced that an experimental immunotherapy that targets a second brake in the immune system dramatically shrank tumors in 18 percent of lung cancer patients, 28 percent of melanoma patients, and 27 percent of kidney cancer patients.
If immunotherapy is proven to work against lung cancer, which kills more people than any other cancer, that will mark a major breakthrough for the strategy, says Jedd Wolchok, a researcher and physician at Memorial Sloan-Kettering who treated Esposito. He and other researchers are now testing these drugs in combination with targeted treatments, chemotherapy, radiation, and other immunotherapies. Experiences such as Esposito's suggest that immunotherapy becomes even more powerful when used together with these other approaches, says Wolchok.
Esposito's experience also shows the potential benefits of signing on for a clinical trial. Fewer than 10 percent of cancer patients enroll in trials, says Neal Meropol, chief of the division of hematology and oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University School of Medicine in Cleveland. He says many mistakenly believe that they may receive a placebo, or dummy pill, instead of treatment. In today's cancer treatment trials, Meropol says, patients in the experimental group typically receive the current standard treatment in addition to what's being tested; those assigned to the control group get standard care.
"We're getting smarter about how clinical trials are designed, and how patients are selected," he says. "The likelihood of deriving a personal benefit from a clinical trial may actually be increasing." Patients can find information about such trials through many sources, including search engines maintained by the National Cancer Institute and by individual cancer centers, and through patient advocacy groups.
Jeff Wigbels is a firm believer. The Atlanta marathon runner, 63, was diagnosed with lung cancer a few years ago, the night before his second child was born. A local doctor told Wigbels that he should start radiation and chemotherapy immediately, but first Wigbels sought a second opinion at MD Anderson. There, doctors helped him enroll in clinical trials and eventually tested Wigbel's tumor for ALK mutations. He tested positive, and started treatment taking aim at these mutations. A week later, Wigbels says, "I went from not being able to swallow food to having no cancer that they could see in my body."