Prescriptive natural killer cell-based immunotherapy for cancer

Leukemia, a cancer of the blood, can only be cured by a stem cell transplant, but 40% of people with this cancer relapse even after a transplant. In patients that do not relapse, natural killer (NK) cells, a type of white blood cell, can kill leukemia cells. We now know that this depends on the specific features of NK cells, and think that directly transplanting NK cells might be a way to treat leukemia and other cancers. The ability of NK cells to recognize and kill tumor cells differs within and among people due to differences in cell surface markers and the signals that they send. If the "go" signals are stronger than the "stop" signals, the NK cell kills the target cancer cell. Understanding and controlling these signals will allow us to make sure that the NK cells that are given to different people are the right match to kill their tumors. This project will study the relative strength of different signals that NK cells receive from leukemia cells. We will study individual NK cell signalling pathways, then how they interact together. This will be done in two ways: by blocking specific interactions, and by presenting the NK cells with select ligands. NK cell activation, and NK cell and cancer cell markers will be quantified using flow cytometry. To better understand these interactions, changes in signalling pathways inside NK cells will be assessed using a technique that lets us watch signalling in real time. This knowledge will enable us to predict and enhance the strength of NK cell killing of leukemia in cell culture experiments and in humanized mouse models. We expect educated NK cells that are not easily inhibited by the cancer cells will be the strongest killers.