Letting Killers Do Their Work
Study at Cincinnati Children’s looks at how the immune system fights cancer cells left behind after a bone marrow transplant
Chaired by Stella Davies, MBBS, PhD, MRCP, director of the Blood and Marrow Transplant Program in the Division of Hematology / Oncology, the study is looking at the best way to use the body’s natural killer cells to destroy residual cancer cells lurking in the marrow after a transplant.
Cells on a Mission
“Natural killer cells are lymphocytes with a special job,” says Dr. Davies. “They are the first responders of the immune system.”
Which, in the case of injury or infection, is a good thing. The killer cells go after the bad cells but spare the healthy ones by means of a special inhibitory interaction.
This inhibitory process is caused by HLA proteins found on a healthy cell’s surface. HLA proteins bind to a receptor on the natural killer cell called the “killer inhibitor receptor.”
“When the killer cell detects the HLA protein,” says Dr. Davies, “it sees it is a friend and it doesn’t attack.”
But sometimes cancer cells also express the HLA protein. When they do, the natural killers are halted, and the cancer cell lives on.
Looking for a Mismatch
Davies hopes to short-circuit this process after a bone marrow transplant so that the killer cell can work on destroying any lingering cancer.
Her study involves children with acute myelogenous leukemia. She is looking for donors with killer inhibitor receptors that are mismatched for the patient’s HLA protein ligand. If they are mismatched, the natural killer cells that enter along with the donor’s bone marrow will be free to do their work.
“When we put them in with leukemia cells that have different HLA proteins, the leash comes off and the natural killer cell attacks,” says Dr. Davies.
The children in the study are considered high-risk because their cancer has already recurred. Dr. Davies hopes the mismatched natural killer cells will attack any straggler cancer cells before they take root, preventing recurrence. She is encouraged by previous studies in adults that show no relapse within 5 years for mismatched donors.
“Perhaps in the future, non-related donors will always be screened for who has the KIR-HLA mismatch, and who does not,” she says. “All it takes is a simple blood test.”
