May 16, 2008 Researchers from The University of Texas M. D. Anderson Cancer Center have found a therapy that effectively kills human leukemia cells in mice using natural killer (NK) cells from umbilical cord blood.
Patrick Zweidler-McKay, M.D., Ph.D., assistant professor of pediatrics from the Children's Cancer Hospital at M. D. Anderson, has shown an effective method for expanding the number of NK cells from a single cord blood unit while retaining the cells' anti-leukemia effects, as presented at the American Society of Pediatric Hematology/Oncology annual conference on May 16.
Previous efforts to expand cord blood have resulted in ineffective NK cells. However, Zweidler-McKay and co-senior investigator Elizabeth Shpall, M.D., professor in M. D. Anderson's Department of Stem Cell Transplantation and Cellular Therapy, have found a novel process to increase NK cells in cord blood more than 30-fold, generating more than 150 million NK cells from one cord blood unit while maintaining their activation to find and kill acute leukemia cells.
When given to mice with aggressive human leukemias, these NK cells reduced the circulating human acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML) cells by 60 to 85 percent.
"Cord blood is a promising source of natural killer cells because the NK cells 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 Zweidler-McKay.
NK Cells Spare Normal Cells While Attacking ALL and AML
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.
Historical transplants used a matched donor's peripheral blood or bone marrow to transplant to a patient. However, in 1988, researchers found cord blood to be another source for stem cell transplantation. These immature stem cells were easier to match to patients, especially those from non-Caucasian ethnicities, and could be stored for use as needed.
Zweidler-McKay's study involves selecting out NK cells from cord blood. As the cord blood is expanded to multiply in number, the NK cells are given a cytokine, interleukin-2, and a target cell, K562, which keep the NK cells active throughout the three week expansion.
Once the process is complete, the NK cells can be transplanted to patients without prior chemotherapy. Zweidler-McKay also 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.
"These NK cells demonstrate significant cytotoxic activity against human AML and ALL cell lines and patient leukemia blasts. Most importantly, mouse models of human AML and ALL were sensitive to NK cell infusions," says Zweidler-McKay. "These results support the evaluation of cord blood-derived NK cells as a potential immuno-therapeutic approach in acute leukemias."
Lead investigator on the study is Dongxia Xing, Ph.D., and Zweidler-McKay and Shpall are senior investigators, all from M. D. Anderson.
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