Jeffrey Miller, M.D., has taken his research on natural killer cells from the laboratory to clinical trials to treat people with blood cancers. (Photo: Scott Streble)
Masonic Cancer Center News
From basic science to second chances
Patients benefit when research moves from the laboratory into the clinic
If you had met Duane Cramer in the spring of 2008, it would have been hard to guess that he had run out of options for treating his acute myelogenous leukemia (AML), a fast-growing blood cancer. Even after four rounds of the strongest chemotherapy and full-body radiation, the Blaine resident didn’t feel sick.
“Nobody who saw me could believe it,” Cramer recalls.
But his blood tests told a different story—cancerous cells remained. Cramer’s doctor, Sarah Cooley, M.D., explains, “His choices were to go on hospice or try something experimental.”
Fortunately, Cramer was at the right place to try an investigational new therapy available through the Masonic Cancer Center, University of Minnesota. Clinical trials using novel treatments based on ideas straight from the lab—generally reserved for patients for whom standard therapies haven’t worked—can offer patients a second chance for remission.
The trial Cramer joined was evaluating the cancer-targeting potential of natural killer (NK) cells, a type of white blood cell that’s part of the immune system. The hope was that an infusion of NK cells from a half-matched related donor would clear out Cramer’s leukemia before he received a hematopoietic cell transplant (HCT) from the same donor.
“The doctors’ honest expectation was that the chances of success were probably somewhere between 20 and 30 percent,” says Cramer. “That was better than no chance. After a family consultation, we decided to go ahead with it.”
Duane Cramer (third from left)— with sons Dan, Brian, and Scott—is “doing great” after treatment through a clinical trial at the University, his doctor says. (Photo: Duane Cramer)
Putting a natural killer to work
Jeffrey Miller, M.D., the Masonic Cancer Center’s associate director of experimental therapeutics, first thought of using NK cells to fight cancer 20 years ago.
At the time, researchers in the field of blood and marrow transplantation—a standard therapy for blood cancers—had discovered that people who relapsed after a transplant could be treated successfully using immune system cells from their original donor. But few scientists had studied NK cells, which protect against viral infections and cancer formation.
Working with Philip McGlave, M.D., deputy director of the Masonic Cancer Center, Miller came up with the idea of capitalizing on NK cells’ tumor-killing ability. Taking an idea like this from the laboratory to clinical trials is known as translational research.
Using NK cells isolated from the blood of normal donors (including themselves), Miller and other researchers in his lab studied the cells’ basic biology.
“A lot of what I did in the first several years in the lab was to try to understand NK cells, how to measure their function, how to see what they do with normal targets and malignant targets,” says Miller, who holds the Roger L. and Lynn C. Headrick Family Chair in Cancer Therapeutics.
He also needed to make sure that the NK cells would not damage the normal cells that are given during a transplant—hematopoietic stem cells, the immature cells that give rise to blood cells.
Miller launched his first clinical trial of NK therapy in 1994 with patients who had received HCTs using their own stem cells. “The reality of translational research is that once you take an idea like this and start testing, it takes a long time,” Miller explains. “So, 10 years later, in 2003, we came to the conclusion that despite successfully activating NK cells in the body, the therapy wasn’t good enough to prevent clinical relapse.”
In the meantime, NK cells were found to have surface receptors that “turn off” when they recognize cells as “self.” Because cancerous cells are actually “self” cells gone awry, NK cells don’t always target them as the enemy. This development prompted Miller to try a new protocol using NK cells from a related partially matched donor instead of using the patient’s own cells.
In 2005 Miller and his team showed that NK cell therapy for people with AML for whom all standard therapies failed could lead to the cancer’s remission. Miller’s group treated 32 people, and 10 achieved complete remission.
Based on those promising results, they developed the next generation of that therapy, which incorporates an NK cell infusion into a partially matched HCT and is designed to cure patients with advanced leukemia. Now 39 patients have been treated—including Duane Cramer.
From bench to beach
Sarah Cooley, M.D., is developing strategies for using natural killer cells to treat solid tumors.
Cramer received his infusion of NK cells on May 6, 2008. The youngest of his three sons, Brian, served as his donor. Because NK cells can be harvested directly from the blood, donating these cells was no more invasive than a blood draw.
Cramer kept an optimistic attitude and told people he was going to beat his cancer.
“He understood the challenges ahead of him and took it one day at a time,” says Cooley, a member of the Masonic Cancer Center and assistant professor in the Department of Medicine’s Division of Hematology, Oncology, and Transplantation. “Now he’s more than one year out, and he’s doing great.”
Cooley, who trained with Miller as a student and is now working to develop strategies to use NK cell therapy to treat solid tumors such as breast cancer as well, leads the leukemia trial through which Cramer was treated.
“We’ve been able to get remission in 50 percent of patients for whom nothing else worked,” she says. “That’s beyond what we expected.”
That’s also a motivator for Miller.
“We feel good that the new therapies we brought from the lab to the clinic are helping people,” he says. “They’re not always curing people … but the only way to be one step ahead is to go back to the laboratory and understand the failures as well as the successes.”
As for Cramer, he believes every day is a blessing. Even though his immune system was still somewhat weakened, he got the go-ahead to travel to Florida last spring.
“I was just happy to be sitting on the beach,” he says.