Polyethylenimine-mediated transfection of human monocytes with the IFN-γ gene: an approach for cancer adoptive immunotherapy

Abstract

Human monocytes (Mo) and monocyte-derived macrophages (MdM) are major effectors in host defense systems against cancer. Their antitumoral activity is dependent upon two processes: recruitment and activation. One of the most powerful activators for these cells is recombinant human IFN-γ (rhIFN-γ). However, when the potential of activated rhIFN-γ 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-γ. Thus repeated injections were required to obtain a clinical response. To overcome this limitation we have developed a gene transfer protocol with IFN-γ cDNA and polyethylenimine 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 model must be improved before clinical use, IFN-γ producing monocytes have potential for adoptive immunotherapy.