Funded in partnership with the Kansas City Chiefs Football Club
Recent successes demonstrate the power of using the immune system clinically to destroy cancer. One such therapy involves the infusion of cells called natural killer (NK) cells. This therapy works well for blood cancers. However, there has been limited success with this therapy against solid cancers. The ultimate goal of our research is to increase this efficacy. NK cell killing occurs when receptors expressed on the NK cells are bound. One of these receptors, Natural killer group 2 member D (NKG2D), plays a critical role in the killing of cancers in both mice and humans. My lab has recently generated data that indicate there is a role for NKG2D-binding partners expressed on NK cells in cancer destruction. We demonstrate that upon activation, human and mouse NK cells express these binding partners on the cell surface. We further show that this alters the secretion of factors that play critical roles in cancer destruction. We propose to test the hypothesis that expression of these NKG2D binding partners alters the ability of NK cells to kill cancer cells and that manipulation of this expression can be used to increase the efficacy of NK cell therapy. We will use mouse models to test this hypothesis with both mouse and human NK cells and cancers. At the completion of these studies we will know 1) whether expression of NKG2D binding partners by NK cells affects NK cancer therapy and 2) whether manipulation of this expression is likely to increase the efficacy of clinical NK therapy.