LIPOSOMAL TRANSFECTION OF HUMAN GAMMA-INTERFERON GENE INTO HUMAN GLIOMA-CELLS AND ADOPTIVE IMMUNOTHERAPY USING LYMPHOKINE-ACTIVATED KILLER-CELLS

The authors evaluated the effect of liposomal transfection of human ga mma-interferon (HuIFN-gamma) gene into human glioma cells and lymphoki ne-activated killer (LAK) cells, alone and in combination. An HuIFN-ga mma gene inserted in a eukaryotic expression vector was entrapped in l iposomes bearing positive surface charges. Liposomal gene transfection induced production of HuIFN-gamma and its secretion in culture medium of human glioma cell lines (SK-MG-1 and U-251 MG), At 4 days after tr ansfection, the cells produced 10 to 50 U/ml of HuIFN-gamma in the med ium, whereby the major histocompatibility complex (MHC) class I and II antigens, as well as intercellular adhesion molecule-1 (ICAM-1), were induced on the glioma cell surface. The growth-inhibiting effect of t ransfection-induced HuIFN-gamma was much stronger in comparison with c ontrol cultures exposed to 500 U/ml of exogenously added HuIFN-gamma. In addition, 20% to 40% growth inhibition was obtained in the glioma c ells when they were treated with LAK cells alone at a 5:1 ratio of eff ector to target cells. Liposomal transfection of HuIFN-gamma gene into human glioma cells combined with immunotherapy using LAK cells was mo re effective than either technique alone. The reinforcement of growth inhibition in the case of combined therapy was quenched by anti-ICAM-1 monoclonal antibody, but not by anti-MHC class I or II monoclonal ant ibodies. These results suggest that the combined effect of liposomal t ransfection of HuIFN-gamma gene plus LAK cells into human glioma cells is a potentially useful therapy for malignant glioma, and that the me chanisms of the reinforcement of growth inhibition are closely related to the expression of ICAM-1 on the glioma cell surface.