Work underway at St. Jude Children's Research Hospital seeks to harnesses the body's own immune cells known as natural killer, or NK, cells to help children battle cancer. NK cells are the immune system's warriors. The cells circulate widely in the body, armed with proteins, called enzymes, capable of delivering a deadly one-two punch to viruses and cancer cells.
The cancer-fighting potential of NK cells was recognized more than 30 years ago, but until recently efforts to exploit them were hampered because there were too few NK cells and those that could be isolated from donors did not always target tumor cells. St. Jude has emerged as a leading center of research into NK cells as a possible cancer treatment, particularly in children. St. Jude investigators are pioneering efforts on both the clinical and basic scientific fronts.
Dario Campana, M.D., Ph.D., St. Jude Oncology department vice chair for laboratory research, led the successful effort to develop techniques to increase the supply of NK cells available to treat patients. He also directed the successful push to re-engineer NK cells to include an artificial cell surface receptor. The receptor helps the NK cells recognize and target acute lymphoblastic leukemia cells.
NK cells now play a role in at least four St. Jude protocols for patients battling different types of leukemia as well as certain tumors of the bone, muscle and connective tissue known as sarcomas. Another St. Jude trial using NK cells is expected to open later this year. Investigators hope NK cells will extend cures by targeting cancer cells that survive chemotherapy.
"Immune therapies, including NK cells, promise to be able to treat patients who are resistant to chemotherapy because they work in a totally different way," Campana said. NK cells are also being tried against a variety of adult cancers, including multiple myeloma, the brain tumor neuroblastoma as well as cancer of the head and neck. Campana's laboratory is collaborating in those efforts with centers in the U.S. and Japan.
Wing Leung, M.D., Ph.D., director of St. Jude Bone Marrow Transplantation and Cellular Therapy, has taken a different approach to developing NK cells as a weapon against cancer. Leung has published a series of papers focusing on the genes for assembling killer immunoglobulin-like receptors or KIRs. KIRs are carried on the surface of the NK cell and help the immune cells recognize and kill cancer cells.
Leung and his colleagues demonstrated KIR proteins help determine whether or not NK cells will target cancer cells. KIR proteins are now the basis of the NK donor selection Leung's laboratory does for both St. Jude and the Children's Oncology Group, the world's largest cooperative childhood cancer research organization. Recently published work from Leung's group hints that tracking tiny variations in the composition of KIR proteins might help further improve NK donor selection.
Earlier this year, Leung was senior author of a study of 10 young St. Jude patients with acute myeloid leukemia (AML) who were each treated with NK cells from a parent. The patients had completed standard therapy with anti-cancer drugs and were in remission when they received the donor NK cells. Nearly three years later, the patients are all alive and cancer free. An editorial that accompanied the report in the Journal of Clinical Oncology praised the St. Jude treatment approach, predicting it could have far-reaching implications for improving AML treatment.
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