Empowering Natural Killer Cells
Conquest - Summer 2008
By Sara Farris
Through mice and tissue studies, M. D. Anderson researchers are discovering new ways to empower natural killer cells to fight leukemia, osteosarcoma and neuroblastoma, according to two presentations at the American Society of Pediatric Hematology/Oncology annual conference in May.
Patrick Zweidler-McKay, M.D., Ph.D., and his colleagues are researching new ways to harness cells to target pediatric leukemia without harmful side effects, such as graft-versus-host disease.
Umbilical cord blood and leukemia
Two clinicians have found a novel process that increases the number of NK cells in an umbilical cord and effectively uses them to kill human leukemia cells in mice.
When given to mice with aggressive human leukemias, these NK cells reduced the circulating human acute lymphocytic leukemia and acute myelogenous leukemia cells by 60% to 85%.
“Cord blood is a promising source of NK cells because they have enhanced sensitivity to stimulation, decreased potential to cause graft-versus-host disease and are available from cord banks throughout the country and world,” says Patrick Zweidler-McKay, M.D., Ph.D., assistant professor in the Division of Pediatrics from the Children’s Cancer Hospital at M. D. Anderson, who made the discovery along with co-investigator Elizabeth Shpall, M.D., professor in M. D. Anderson’s Department of Stem Cell Transplantation and Cellular Therapy.
Graft-versus-host disease is a common side effect of patients receiving stem cell transplants, which results when the T cells in the transplanted blood react against the patient’s own cells. This disease can become fatal if it’s unable to be controlled. NK cells operate differently from T cells, leaving normal cells alone while targeting and killing the cancerous cells.
Once the NK cells are put through this novel process, they can be transplanted to patients without prior chemotherapy. Zweidler-McKay predicts this type of transplant could be used for adults who have already had a transplant or for those adult and pediatric patients who aren’t candidates for other stem cell transplants due to blood counts or illness.
Natural killer cells and epigenetic drugs
A combination therapy has the potential to treat different types of childhood cancer, including osteosarcoma, certain leukemias and neuroblastoma, while possibly sparing young patients from more difficult therapies such as stem cell transplant or more toxic chemotherapy.
Dean Lee, M.D., Ph.D., assistant professor in the Division of Pediatrics from the Children’s Cancer Hospital, has found that combining the epigenetic drug MS-275 with NK cells makes osteosarcoma cells more sensitive to NK cells while making the NK cells more lethal to the tumor. Though a rare pediatric cancer, osteosarcoma is the most common bone cancer found in children.
“Traditional chemotherapy drugs kill any fast-growing cells like cancer, but they also kill healthy fast-growing cells like hair, bone marrow and mucous membranes, making the drugs very toxic,” says Lee, senior investigator on the study. “There’s a new class of drugs that takes cells that aren’t properly regulated and makes them behave. In our study, we found that these drugs make tumor cells more recognizable and vulnerable to natural killer cells.”
The study also found similar responses from acute myelogenous leukemia and neuroblastoma, by combining NK with different inhibitors, NPI-0052 and Bortezomib. Additional research is being conducted on acute lymphocytic leukemia, the most common cancer in children, and medulloblastoma, the most common brain cancer in children.
Lee hopes these findings will lead to a clinical trial for patients.
“By applying what we’ve found from our study, we hope to improve our treatment for many cancers, but not by giving more NK cells or more toxic chemotherapy,” Lee says. “Instead, we want to marry the two therapies to improve each other and provide a more effective, less toxic treatment for our patients.”
Funding for the study came from M. D. Anderson and the For Julie Foundation.
Conquest - Summer 2008