Augmentation of antitumor immunity by tumor cells transduced with a retroviral vector carrying the interleukin-2 and interferon-gamma cDNAs

leading to tumor rejecti~n.~~~.’~ The synergistic interaction of cytokines has been shown in several biologic systems. By transducing a tumor cell with the cDNA’s for both IL-2 and IFN-y, we have attempted to induce increased antitumor immunity by activating the afferent as well as the efferent arm of the immune response. IFN-y should act by enhancing the immunogenicity of the target cell and by activating nonspecific cytotoxic effector cells, whereas IL-2 should provide the costimulatory signal necessary to activate and expand cytotoxic T cells, presumably present in close proximity to the transduced tumor ~ells.~’-~~ Because mixing two tumor cell populations (each population secreting one cytokine) could lead to preferential elimination of one of the populations” and, thus, to the premature cessation of the effects of one cytokine, we have decided to express both cytokines by the same tumor cell to increase cellular antitumor response in vivo. Because a single transduction step providing signals for optimum primary rejection would be desirable for in vivo use, we have developed double cytokine retroviral vectors carrying both IL-2 and IFN-y genes or IL2 and GM-CSF genes and, as controls, single cytokine ret