Natural killer (NK) cells play critical roles in host defense against infections and malignant diseases by secreting immuno-regulatory cytokines and by killing infected or transformed cells. We hypothesized that targeting negative regulators of NK cell function will lead to a novel cancer immunotherapy similar to the cases of targeting negative regulators of T cells.
When NK cells encounter tumor cells, their activating receptor is stimulated by tumor-associate antigen. But simultaneous interaction between inhibitory killer-cell immunoglobulin-like receptor (KIR) and tumor ligands, predominantly human leukocyte antigen (HLA-C) deactivates the NK cells. NK cell activity can be restored by KIR/HLA inhibitors. KIR2DL1/2/3 and HLA-C are candidates of target molecules.