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Building on expertise

A research team led by Jeffrey Miller, M.D., builds on more than 20 years of experience to create better cancer therapies using natural killer cells. (Photo: Scott Streble)

U scientists keep improving the use of natural killer cells against cancer

All humans, healthy or not, have cells called “natural killers” that help make up our immune systems. When cells become damaged, infected, or cancerous, NK cells recognize changes on those cells and kill them.

So, for people with cancer that continues to grow, why don’t NK cells destroy the tumors?

“When tumors start to grow, they suppress the immune system,” explains Jeff rey Miller, M.D., deputy director of the Masonic Cancer Center, University of Minnesota and director of its Cancer Experimental Therapeutics Initiative (CETI). “There’s no way to know how many times NK cells protect someone from cancer. We only know when they fail.”

Miller is just one of the scientists at the University studying NK cells and how best to use them in cancer therapies. In fact, the team is discovering ways NK cells can be activated and directed to seek and destroy tumor cells. It’s exciting work because, well, it works.

“I started studying NK cells when I came to the U in 1991, exploring what capacity NK cells have to become cancer scavengers,” says Miller. “We’ve treated hundreds of patients in clinical trials since then and have defi nitely had success. But we know we can improve outcomes for patients.”

In one clinical trial, for instance, Miller infused patients afflicted with resistant or relapsed acute myeloid leukemia (AML) with NK cells from a healthy donor and saw a 30 percent remission rate—definitely a positive outcome.

“What we know is that we can put stubborn cases of AML into remission,” says Sarah Cooley, M.D., a Masonic Cancer Center member and an assistant professor of hematology, oncology, and transplantation. “Now we’re trying to add different receptors to the NK cells to get a higher percentage of patients into remission.”

Sarah Cooley, M.D.

‘Team science’

Cooley is part of what Miller calls the “team science” approach: developing a critical mass of investigators focused on one area of research. Miller oversees 20-plus researchers, including University of Minnesota Medical School staff, laboratory workers, and postdoctoral fellows. To make sure everyone stays abreast of work going on in other labs, Miller holds regular meetings and presents clinical trial results to keep the lab team excited about what it’s doing.

“You have to build on your expertise to bring something meaningful to the cancer community,” explains Miller. “NK cell research is one of the Masonic Cancer Center’s specialties.”

Under that NK-cell research umbrella, the scientists investigate separate but related projects. Cooley focuses on two main areas: using donor NK cells, typically from a halfmatched family member, and studying the roles of different receptors on NK cells. She is also part of a large grant from the National Cancer Institute that Miller oversees that examines the role of NK cells in transplants from unrelated donors.

In another nearby lab, Dan Kaufman, M.D., Ph.D., cultivates NK cells from human pluripotent stem cells. He recently developed a more efficient, cost-effective process for deriving NK cells from these stem cells, which could pave the way for a larger-scale production effort.

“Our ability to now produce large numbers of cytotoxic [cell-killing] NK cells could have far-reaching effects for future cancer therapies,” he says. “And it may also be possible to engineer the cells with antitumor and antiviral receptors to provide off-the-shelf products for cancer treatments. That’s the goal.”

Dan Kaufman, M.D., Ph.D., believes that by modifying natural killer cells, researchers could target and destroy more types of cancer. (Photo: Scott Streble)

Fine-tuning the formula

With each new discovery, the team develops a better understanding of how NK cells can be manipulated to attack and kill cancer cells; then they tinker with the formula and try again.

Miller and gynecologic surgeon Melissa Geller, M.D., M.S., are currently taking a new approach in a clinical trial for women who have ovarian cancer by infusing donor NK cells directly into the patients’ abdominal cavities instead of into the bloodstream as usual.

“We’re hoping we can improve the outcomes by putting NK cells into close proximity to the cancer,” Miller explains. “The goal for the study is to find the donor NK cells in the patient’s blood after seven or 14 days. If we can detect them in a blood test, we know the infused NK cells have expanded successfully.”

Like most clinical trials, the ovarian cancer study is expensive, so right now the team is starting with one infusion per patient. But if the results indicate that it’s a successful therapy for ovarian cancer, future plans may involve infusions every three months for the first year of treatment.

“These are the kinds of ideas we always have in the back of our minds,” says Miller. “We’re not there yet, but that could be the next step.”

Crossing the valley

Real advances in cancer treatment require not only the brightest thinkers but also the money to transform their ideas into reality— from start to finish.

Kaufman likens running a research laboratory to running a small business: “You’re always looking to raise capital.” He notes that the period between the successful conclusion of animal studies and the beginning of human clinical research is known among scientists as “the valley of death.”

“That’s the time when projects can stall, or even die,” he explains. “It’s very hard to get funding for that work.”

That’s the reason the Masonic Cancer Center created CETI in 2011. Headed by Miller and funded by Minnesota Masonic Charities and other philanthropists, CETI is designed to move the most promising lab research into clinical studies faster. Cooley, Geller, and Miller have all received support from CETI.

“[Miller] has formalized our disparate group of researchers into a strong NK cell research team,” Cooley says. “He’s built a pipeline that helps us all go from preclinical testing to Phase I clinical trials, and he channels the funds where they’re needed most. And while we’re all at diff erent places with our work, he keeps us working as a united team with a common goal: how can we use NK cells to cure cancer?”

To find out how your support can help to advance NK cell research, contact Cathy Spicola at 612-625-5192 or

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