Immuno-therapy has taken a lead among the new cancer therapeutic approaches. It is one of the most promising new therapeutic approaches that exploit the innate immune mechanism of an individual to fight against a certain disease.

Natural killer (NK) cells are a form of cytotoxic lymphocytes which constitute a major portion of the innate immune system. NK cells have tumor cytotoxic properties independent of tumor specific antigens and have been shown in murine models to control and prevent tumor growth and dissemination. Inactivation of NK cells potentially allows cancer cells to evade host NK-cell-mediated immunity. Ligation of killer immunoglobulin like receptors (KIRs) by MHC class I on both normal and malignant tissues suppresses the function of NK cells.

The present invention relates to treating cancer and other hyperproliferative disorders by administering an enriched composition of allogeneic or autologous (KIR/KIR ligand incompatible) NK cell population. This enriched composition can potentially override the inactivation of NK cells by self HLA molecules or MHC class I expressing tumors. Claims cover compositions of enriched NK cell populations and method of treating malignancies or prevent recurrence of malignancies and treating any hyperproliferative disorders with these enriched compositions. Claims also cover a method to sensitize malignancies to NK cell TRAIL-mediated killing by pretreatment with bortezomib.