Design of artifical tumor cells to induce Natural Killer cell proliferation (42.13)

Abstract

Abstract Natural Killer (NK) cells respond to tumor cell contact by cellular cytotoxicity, cytokine release and proliferation upon recognition of the tumor cells by an array of co-activating receptors such as Natural Cytotoxicity Receptors (NKp30, NKp44, NKp46), NKG2D, CD2, NKp80 and CD16 (binding to tumor cell reactive antibodies). Responsiveness of NK cells to tumor cells depends on complicated parameters of the individual's immune system and, if evaluating NK cell function in coculture of NK cells with tumor cell lines, requires maintenance culture of those cell lines and will cause further variation of experimental conditions. We designed artifical tumor cells to tightly control human NK cell culture conditions. Tumor cells are mimicked by large magnetic spheres ("MACSiBead Particles") coated with ligands to activating NK cell receptors. Combinations of antibodies to NKp46 (CD335), NKG2D (CD314), Nkp80, CD2 have been evaluated as ligands and were feasible to induce a median 30 to 100 fold expansion of MACS isolated human NK cells within 2 to 3 weeks. We demonstrated that cellular cell culture components such as tumur cell lines or allogeneic peripheral blood mononuclear cells (PBMC) are not required to induce significant NK cell proliferation and that artifical tumor cells (cell sized antibody coated magnetic particles) can be used instead and may provide a tool for NK cell proliferation for either diagnostic / analytical or NK cell therapy production purposes.