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目的:为了探讨脂质体介导的IL-2基因体内基因转移的可行性及对荷瘤小鼠全身免疫功能的激活作用及诱导细胞因子产生的效果。方法:将脂质体分别包裹IL-2基因、空白质粒及PBS后,直接注射至黑瘤体内,10d后无菌取出小鼠脾细胞,诱导并检测肿瘤特异性杀伤细胞(CTL)活性、LAK活性及细胞因子的含量,用抗MHCIa单抗检测腹腔巨噬细胞的MHCI类分子的表达。结果:瘤体内注射脂质体包裹的IL-2基因后,小鼠脾CTL细胞活性明显高于瘤体内注射脂质体包裹空白质粒及PBS的对照组,其脾淋巴细胞LAK活性、诱导IFN-γ等细胞因子的含量及表达MHCIa分子的水平均有相应的提高。结论:瘤体内注射脂质体包裹的IL-2基因后,通过在原位转染肿瘤细胞,增强了肿瘤细胞的免疫原性,诱导机体产生肿瘤特异性的CTL以及提高机体非特异性的抗肿瘤免疫反应,发挥抗肿瘤作用。本研究为肿瘤的基因治疗的研究和应用提供了较实用的方法。
Objective: To investigate the feasibility of liposome-mediated gene transfer of IL-2 gene in vivo and the activation of systemic immune function in tumor-bearing mice and the induction of cytokine production. METHODS: Liposomes were separately encapsulated into IL-2 gene, blank plasmid and PBS and injected directly into the melanoma. After 10 days, the mouse spleen cells were aseptically removed to induce and detect the activity of tumor specific killer cells (CTL) and LAK. The content of activity and cytokines was detected by the anti-MHCIa monoclonal antibody in the expression of MHC class I molecules in peritoneal macrophages. RESULTS: After intratumoral injection of liposome-encapsulated IL-2 gene, the activity of spleen CTL cells in mice was significantly higher than that in tumor-injected liposomes-encapsulated blank plasmid and PBS control group. LAK activity of spleen lymphocytes and induction of IFN- The content of γ and other cytokines and the level of expression of MHC Ia molecules have been correspondingly improved. Conclusion: After intratumoral injection of liposome-encapsulated IL-2 gene, the in situ transfection of tumor cells enhances the immunogenicity of tumor cells, induces tumor-specific CTL production, and enhances the body’s non-specific antitumor activity. The immune response exerts an anti-tumor effect. This study provides a more practical method for the study and application of tumor gene therapy.