Researchers at the Fred Hutchinson Cancer Research Center have melanoma under their microscopes, and they’re approaching the deadly cancer in new and promising ways.
Though rare, melanoma is among the fastest-rising of cancers, and surprisingly, the gloomy Pacific Northwest has some of the highest rates. It could be because people go without sun for most of the year, don’t develop protective melanin, then get burned in the summer; or it could be the region’s fair-skinned Scandinavian heritage — scientists aren’t sure.
When it comes to melanoma, nothing is a sure thing, especially when it comes to treatment. But new techniques in immunotherapy may offer hope of a better outcome in the future.
Harvesting fighter cells
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“The field of immunotherapy has exploded. We’re in a revolution in cancer treatment right now,” says Dr. Sylvia Lee, an oncologist and researcher at Fred Hutchinson who practices through the Seattle Cancer Care Alliance.
Lee is studying tumor-infiltrating lymphocyte (TIL) therapy, and in July 2013, Fred Hutchinson and the Seattle Cancer Care Alliance became one of just four sites in the country to offer it to patients on a trial basis.
So far, 13 patients in the Seattle program have enrolled and two have been treated. Response to the therapy can take a year for maximum results to display, but the first patient has had a 37 percent reduction in tumor size after three or four months, and the second has had a 25 percent reduction in six weeks. Both patients had not responded to other types of immunotherapy.
TIL therapy, also known as adoptive cell transfer, works by harvesting cancer-fighting immune system cells (T cells) from melanoma patients, growing them in a lab, and infusing them back into the patient. Other T-cell therapies work similarly, but what distinguishes TIL is that it uses only T cells that have already attached themselves to the patient’s melanoma and show signs of being able to fight it. In melanoma patients, not all of them do, since the cancer suppresses the immune system.
Lee’s protocol isolates T cells that have attached themselves to an excised tumor. “The idea is that those T cells are the ones that can recognize the melanoma and have already traveled to it,” she says. She grows the cells in a lab for three to five weeks while the tumor sample is frozen. Then they are put to the test: The tumor sample is thawed and the new T-cell army is deployed to fight it. Lee chooses only T cells that fight the tumor the best during this trial to be infused into the patient.
But first, the patient must undergo seven days of chemo — not to fight the melanoma, but to wipe out an immune system that has been too damaged by it to do its job. After chemo, the strong cancer-fighting T cells are infused. Then she adds Interleukin 2, a growth factor that causes the cells to grow and proliferate.
It’s a one-time therapy — after a two-week hospitalization, the patient goes home and the new T cells keep up their work.
It’s not a panacea. Data from previous trials shows that only about 60 percent of patients generate enough healthy T cells to be used in the therapy. Part of the problem is the compromised immune system caused by the cancer, and sometimes previous treatments have created lots of dead or dying cells in the tumor that don’t draw T cells. Also, older patients often have a weaker immune response. Lee hopes that over time, scientists will find ways to increase the harvesting of healthy cells.
The therapy may eventually be used for lung and other kinds of cancer, too, Lee says. Many immunotherapies are tried on melanoma first because it is one of the cancers most easily recognized and fought by the immune system, but if a therapy works, that suggests it may be effective against other cancers.
Targeted T-cell therapy
Instead of using a patient’s own T cells to fight cancer, Dr. Aude Chapuis, another oncologist at Fred Hutchinson working on immunotherapy, is using T-cell receptors from healthy donors to do the job. She started a lab of her own at Fred Hutchinson in July as part of the center’s immunology department. Lee is also part of this department, which is directed by Dr. Phil Greenberg.
T-cell therapy has been around for more than 20 years, but it didn’t work very well at first, Chapuis says. T cells were removed, grown in culture and returned to patients to help fight cancer, but they didn’t stick around long, and even when they did, the cancer usually returned. Today’s targeted therapies work better.
“We’ve learned a lot of things over 20 years,” Chapuis says.
The T-cell receptors of cancer patients often do a poor job of recognizing their cancer-cell targets. In a clinical trial for leukemia patients, Chapuis is trying a new method. The therapy is being used in a trial for patients who have undergone a bone-marrow transplant, in which their unhealthy immune system cells have been removed and replaced with donor cells.
Before the donor T cells are infused into the patient, they are genetically modified in a way that is designed to make them work better if the patients’ cancer returns. In a special lab in Los Angeles, a strong cancer-fighting protein is inserted into the bone-marrow donors’ T cells.
Finding this uber-protein is part of Chapuis’ research. For the current trial, she screened thousands of T cells to find the strongest protein, then cloned it. After the bone-marrow donors’ T cells are modified to express this super protein, they are infused into the patient. Then, if these cells encounter a tumor, the protein will activate to kill it.
“Sometimes a patient’s T cells don’t work right. This is a way to redirect T cells to recognize their own cancer and kill it,” Chapuis says.
So far, the technique is being used only on leukemia patients, but there are plans to try it for other cancers, including melanoma, lung cancer and ovarian cancer.
Unlike chemo, which kills not only cancer cells but a host of healthy ones, T cells — when they work right — recognize and kill tumor cells while leaving healthy tissue unharmed.
“It’s exciting to be part of a team that creates a new cancer therapy. It’s obvious that this is the way of the future,” Chapuis says.
For now, immunotherapies such as Chapuis’ and Lee’s must travel down separate medical-obstacle courses, each proving its worth in labs and carefully controlled clinical trials until it establishes an acceptable level of safety and effectiveness. But in the future, combination trials are likely in immunotherapy, providing more options and greater hope for patients.
Teresa Meek is a Seattle freelance writer and editor. Her work has appeared in The Miami Herald, Newsday, the St. Petersburg Times and The Baltimore Sun.