The researchers then genetically modified the growing NK cells so they carried on their surface an artificial receptor that made them particularly aggressive and effective killers that attacked only leukemic cells. A receptor is a protein that binds to a specific target molecule. The artificial receptor on the NK molecule was designed to recognize a protein called CD19, which is found on the surface of leukemic cells. When the receptor bound to CD19 on leukemic cells, it set off a reaction that super-charged the killing activity of the NK cell.
"By developing a technique for cultivating large numbers of NK cells from a small blood sample, we made it practical to consider them a potential treatment against many different types of cancer," Campana said. "By genetically modifying NK cells so they expressed the CD19 receptor, we made them specifically effective against ALL cells."
A potential clinical application for the technology developed in this study is in leukemia patients who are treated with hematopoietic (blood cell-forming) cell transplantation. In this case, NK cells will be derived from the transplant donor, expanded and genetically modified. These modified NK cells will then be infused into the patient after the transplant in order to eliminate residual leukemic cells. In another application, NK cells could be obtained from a patient while in remission and then reinfused after genetic modification if the patient suffers a resurgence of the leukemia.
"We look forward to seeing this strategy being added to the management of children with ALL," said Chihaya Imai, M.D., the postdoctoral student who did most of the work on this project.