Feb 29, 2008

Natural Killer Cells

There are killers within us. The human immune system contains natural killer (NK) cells that protect us by attacking cancer cells and viral pathogens. These NK cells are a specific type of lymphocyte that travels the bloodstream looking for cells that don't belong. Viruses are easy to spot, but cancer cells arise from our own bodies so sometimes NK cells don't recognize them as foreign and allow malignancies to spread unchecked.

Daniel Weisdorf, M.D., and Jeffrey Miller, M.D., weren't willing to let the story end there. Believing that natural killer cells hold great promise in the fight against cancer, they began research into using cellular immunotherapy techniques - stimulating or supplementing the patient's immune system - to treat advanced cancer. Specifically, Weisdorf and Miller are investigating whether donor NK cells can be used as "soldiers for hire," tiny but powerful weapons against the recipient's malignancy.

Weisdorf and Miller are Senior Investigators in the Adult Blood and Marrow Transplant Program at University of Minnesota Medical Center, Fairview, and have developed a novel therapy derived from donor transplants. "We realized that a big component of allogeneic (donor) stem cell transplants was a cellular attack from the donor cells on the cancer that remained after chemotherapy," says Weisdorf. With that in mind, the patient is first given immunosuppressive chemotherapy, both to fight the disease and to prepare the immune system to not reject the transplanted cells. This is followed by an infusion of natural killer cells taken from a related donor, coupled with injections of interleukin-2, a lymphocyte-stimulating hormone that helps replenish the patient's depleted immune system. "The donor natural killer cells aren't tissue-typed - matched with the patient - so they attack the malignancy," says Weisdorf. At the same time, they're able to organize the body's own immune system to recognize the bad cells.

So far, Weisdorf, Miller and their colleagues have used this unique treatment on patients with acute leukemia that has resisted other therapies. The results have been positive, with twenty percent of patients going into complete remission. This is promising enough to start trials using cellular immunotherapy on other types of leukemia. They are also recruiting patients for a trial using allogeneic NK cell therapy on non-Hodgkin's lymphoma. In this treatment, the donor cells are supplemented with a synthetic anti-tumor antibody.

In addition, they are collaborating with colleagues in other specialties to investigate the use of natural killer cells against non-hematological cancers, including breast and ovarian cancer.

Weisdorf hopes that what they're learning now may also lead to safer donor transplants in the future. Genetic testing and a more thorough understanding of natural killer cells will help physicians choose well-matched donors, with less chance of rejection and better odds for a successful NK attack which will strengthen the potency of a transplant. Holding promise for safer transplants and better outcomes for patients, these natural killers may save countless lives.

Jeffery Miller, MD	Daniel Weisdorf, MD