POLYETHYLENIMINE-MEDIATED TRANSFECTION OF HUMAN MONOCYTES WITH THE IFN-GAMMA GENE - AN APPROACH FOR CANCER ADOPTIVE IMMUNOTHERAPY

Human monocytes (Mo) and monocyte-derived macrophages (MdM) are major effectors in host defense systems against cancer. Their antitumoral ac tivity is dependent upon two processes: recruitment and activation. On e of the most powerful activators for these cells is recombinant human IFN-gamma (rhIFN-gamma). However, when the potential of activated rhI FN-gamma was evaluated in clinical trials by ex vivo adoptive cellular immunotherapy protocols, the major problem was the short duration of ex vivo activation by rhIFN-gamma. Thus repeated injections were requi red to obtain a clinical response. To overcome this limitation we have developed a gene transfer protocol with IFN-gamma cDNA and polyethyle nimine so as to obtain an efficient, long-lasting autocrine cytocidal activation in transfected human Mo/MdM. We show, by clonogenic assays, that efficient transfection and tumoricidal activity can be obtained by this method in human monocyte populations. Although the proposed mo del must be improved before clinical use, IFN-gamma producing monocyte s have potential for adoptive immunotherapy.