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University of Minnesota
April 27, 2009
Researcher Dan Kaufman has produced potent cancer-fighting immune cells from human embryonic stem cells.
Photo: Emily Jensen
Home page image: James Dutton
Experiments in mice open new avenue for cell-based cancer therapy research
By Deane Morrison
In a study of human tumors growing in mice, University of Minnesota researchers have found that immune cells derived from human embryonic stem cells (hESCs) completely eliminated the tumors in 100 percent—13 of 13—of mice tested.
In contrast, similar immune cells derived from human umbilical cord blood cells cleared away tumors in only five of 13 mice.
"This is the first demonstration of anti-cancer activity in a living organism by cells derived from human embryonic stem cells," says study leader Dan Kaufman, an associate professor of medicine and associate director of the University's Stem Cell Institute. "The superior performance by cells with an hESC lineage points to a crucial role for hESCs in developing new cell-based cancer therapies."
Kaufman and his colleagues also found that mice injected with hESC-derived cells had fewer metastases. And hESC-derived cells did a better job of killing laboratory cultures of human leukemia and solid tumors of breast, prostate, and testicular cancer. The study is published in Blood.
The cancer-killing immune cells are called natural killer (NK) cells. They are endowed with an ability to home in on cancer cells and destroy them, but the body's supply of them too often proves inadequate. For this reason, cancer researchers want to grow large numbers of highly potent NK cells, or cells with similar abilities, that can efficiently kill tumors while escaping destruction by a patient's immune system.
One step toward achieving that goal is to identify the best source from which to produce NK cells. hESCs may become an important supplier in future clinical therapies that have previously used NK cells isolated from normal adult blood or umbilical cord blood.
The key to the effectiveness of the hESC-derived NK cells lies in their maturity, the researchers say. Populations of those cells contained nearly all mature, fully competent NK cells, whereas populations of cells derived from umbilical cord blood contained large numbers of immature NK cells.
Nevertheless, hESCs present problems as a source of NK cells for clinical use, the researchers say. For one thing, any cells derived from an unrelated donor's hESCs could be eliminated by the patient's immune system. Also, says Kaufman, scaling up the production of hESCs to supply enough to treat a person, rather than a mouse, will require a concerted effort by physicians and researchers.
However, a recently developed technique holds potential for generating NK cells from a patient's own cells. It involves genetically reprogramming adult cells into cells very similar to hESCs. These cells—called induced pluripotent stem (iPS) cells—have already been used to derive blood cell-forming stem cells, so using them to produce natural killer cells is a strong possibility, the researchers say.
Work along those lines would only intensify research on hESCs, says Kaufman, because in order to coax iPS cells into differentiating into mature NK cells, researchers will need to know much more about how "the real McCoy" does it. Further work must include studies of many hESC cell lines in addition to the single cell line used in the current research.
"hESCs provide a gold standard to compare iPS cells to," Kaufman says. "We want to use all available avenues to determine the optimal source of cells to treat cancer."