Activation of systemic immune effectors and induction of cytokine production by direct intratumoral injection of IL-2 DNA liposome

摘要

To identify the feasibility of liposome mediated IL-2 gene transfer in vivo and determine its effect on activation of systemic immune effectors and induction of cytokine production, we prepared cationic liposome encapsulated IL-2 DNA, plasmid DNA or PBS, and injected it into B16F10 tumor mass directly. Ten days later, the splenocytes of the treated mice were used to detect the cytotoxicity of cytotoxic T lymphocytes (CTL), LAK activity and the level of cytokine. The MHC class-II molecules expressed on the peritoneal macrophage was determined by monoantibody with FACS. After intratumoral injection of IL-2 DNA liposome, the potent CTL activity of the splenocytes from the treated mice could be induced. The splenic NK and LAK activity increased markedly. High level of IL-2, IFN-gamma secreted by the splenocytes was also detected. Peritoneal macrophage expressed much more MHC Ia molecules. Those results demonstrated that direct intratumora1 injection of IL-2 DNA liposome could transfect IL-2 gene into tumor cells in situ, altering the immunogenicity of the tumor cells, inducing tumorspecific and non-specific antitumor responses and then exhibiting potent antitumor effect. The results offer fundamental available data for gene therapy of malignant tumor.