Fall 2013 Masonic Cancer Center News A publication for those who support Building on expertise cancer research, education, and care U scientists keep improving the use of natural killer cells against cancer at the University All humans, healthy or not, have cells called “natural killers” that help make up our immune of Minnesota 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 Photo by Scott Streble 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. Why are more women with breast cancer “I started studying NK cells when I choosing double came to the U in 1991, exploring what mastectomies? capacity NK cells have to become page 4 cancer scavengers,” says Miller. “We’ve U fi nding answers treated hundreds of patients in clinical about higher cancer trials since then and have defi nitely had rates on Iron Range page 5 success. But we know we can improve outcomes for patients.” Songwriter’s legacy li s U bone cancer In one clinical trial, for instance, Miller A research team led by Jeff rey Miller, M.D., builds on more than research up, up, up 20 years of experience to create better cancer therapies using continued on page 2 page 6 natural killer cells. Building on expertise (continued from cover) infused patients afflicted with resistant or “You have to build on your expertise to relapsed acute myeloid leukemia (AML) bring something meaningful to the cancer with NK cells from a healthy donor and saw community,” explains Miller. “NK cell a 30 percent remission rate—definitely a research is one of the Masonic Cancer positive outcome. Center’s specialties.” “What we know is that we can put stubborn Under that NK-cell research umbrella, the cases of AML into remission,” says Sarah scientists investigate separate but related Cooley, M.D., a Masonic Cancer Center projects. Cooley focuses on two main areas: member and an assistant professor of using donor NK cells, typically from a half- hematology, oncology, and transplantation. matched family member, and studying the “Now we’re trying to add different receptors roles of different receptors on NK cells. She to the NK cells to get a higher percentage of is also part of a large grant from the National patients into remission.” Cancer Institute that Miller oversees that examines the role of NK cells in transplants ‘Team science’ from unrelated donors. Cooley is part of what Miller calls the “team In another nearby lab, Dan Kaufman, science” approach: developing a critical M.D., Ph.D., cultivates NK cells from mass of investigators focused on one area of human pluripotent stem cells. He recently research. Miller oversees 20-plus researchers, developed a more efficient, cost-effective including University of Minnesota Medical process for deriving NK cells from these Sarah Cooley, M.D. School staff, laboratory workers, and stem cells, which could pave the way for a postdoctoral fellows. To make sure everyone larger-scale production effort. stays abreast of work going on in other labs, “Our ability to now produce large numbers Miller holds regular meetings and presents of cytotoxic [cell-killing] NK cells could clinical trial results to keep the lab team have far-reaching effects for future cancer excited about what it’s doing. therapies,” he says. “And it may also be possible to engineer the cells with Photo by Scott Streble antitumor and antiviral receptors to provide off-the-shelf products for cancer treatments. That’s the goal.” 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’ Dan Kaufman, M.D., Ph.D., believes that by modifying natural killer cells, researchers abdominal cavities instead of into the could target and destroy more types of cancer. bloodstream as usual. 2 “We’re hoping we can improve the What’s the appeal outcomes by putting NK cells into close of natural killer cells? proximity to the cancer,” Miller explains. “The goal for the study is to fi nd the donor While cancer treatments like NK cells in the patient’s blood a er seven chemotherapy and radiation damage or 14 days. If we can detect them in a blood cells indiscriminately, natural killer (NK) test, we know the infused NK cells have cells target only cancerous cells, leaving expanded successfully.” normal cells unharmed. Like most clinical trials, the ovarian cancer NK cells can be collected from a donor’s study is expensive, so right now the team is blood, or they can be made in greater starting with one infusion per patient. But quantities from pluripotent stem cells. if the results indicate that it’s a successful Physician-researchers also like that NK therapy for ovarian cancer, future plans may cell therapies don’t require as close of a involve infusions every three months for the genetic match between the recipient and To fi nd out how your fi rst year of treatment. donor as some other immunotherapies. support can help “These are the kinds of ideas we always to advance NK cell There’s also potential to manipulate have in the back of our minds,” says Miller. research, contact them to target certain types of tumors. “We’re not there yet, but that could be the Cathy Spicola at Today NK cells are good at killing blood next step.” 612-625-5192 or cancers such as leukemia, says Dan [email protected]. Kaufman, M.D., Ph.D., but adding specifi c Crossing the valley receptors to the cells could help them Real advances in cancer treatment require work be er against solid tumors as well. not only the brightest thinkers but also the money to transform their ideas into reality— from start to fi nish. 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 “[Miller] has formalized our disparate group funding for that work.” of researchers into a strong NK cell research That’s the reason the Masonic Cancer team,” Cooley says. “He’s built a pipeline Center created CETI in 2011. Headed by that helps us all go from preclinical testing Miller and funded by Minnesota Masonic to Phase I clinical trials, and he channels Charities and other philanthropists, CETI the funds where they’re needed most. And is designed to move the most promising lab while we’re all at diff erent places with our research into clinical studies faster. Cooley, work, he keeps us working as a united team Geller, and Miller have all received support with a common goal: how can we use NK from CETI. cells to cure cancer?” 3 Ask the expert: Why are more women getting double mastectomies to treat breast cancer when it only aff ects one breast? First of all, is it really true that more Angelina Jolie recently told the world breast cancer patients are opting for about her double mastectomy, and she double mastectomies? didn’t have cancer. Does that make sense? Yes, multiple studies have shown that to be I actually like the Angelina Jolie story and the case. We don’t really know why. Some hope it gets out even more, because she women may choose a double mastectomy did it the right way. One of her doctors followed by reconstruction surgery to ensure discovered a red fl ag in her family history— symmetry. But I think a lot of women do it her mother had ovarian cancer at a young because they believe it will improve their age. So Jolie underwent genetic counseling chances for long-term survival—and that and testing and was found to carry the concerns me. BRCA gene that is associated with a very Todd Tuttle, M.D. high incidence of breast and ovarian cancer. A double mastectomy won’t improve Her decision to undergo prophylactic cancer survival rates? mastectomy was very reasonable. Women Research has not shown a survival benefi t should talk with their doctors and get as with the second mastectomy. Most women’s much information as possible before making understanding of their cancer risk in the that decision. other breast is grossly exaggerated. For a woman with cancer in one breast, the Todd Tuttle, M.D., is a member of the 10-year risk of getting a cancer in the other Masonic Cancer Center and a surgical breast is only about 4 to 5 percent.