摘要
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 identify the feasibility of liposome mediated IL-2 gene tansfer in vivo and determine its effects on activation of systemic immune effectors and induction of cytokine production. Metbods:IL-2 DNA, plasmid DNA or PBS was encapsulated into liposome,and was injected into B16-F10 tumor mass directly. Ten days later , the splenocytes from the treated mice were used to detect the cytotoxicity of CTL and LAK activity and the levels of cytokines. The MHC class- I molecular expression on the peritoneal macrophage was determined by monoantibody with FACS. Results: After intratumoral injection of IL-2 DNA , the potent CTL activity of the splenocytes from the treated mice could be induced. The splenic NK and LAK activity was increased markedly. High levels of IL-2 and IFN-γ secreted by splenocytes were also detected. Peritoneal macrophages expressed much more MHC Ia molecules. Conclusion : These results demonstrate that direct intratumoral injection of IL-2 DNA-liposome can transfect IL-2 gene into tumor cells in situ , alter the immunogenicity of the tumor cells , induce tumor-specific and non-specific antitumor response and then exhibit potent antitumor effect. The results offer a practical method for gene therapy of malignant tumor.
出处
《第二军医大学学报》
CSCD
北大核心
1996年第1期15-18,共4页
Academic Journal of Second Military Medical University
基金
国家自然科学基金
优秀中青年人才专项基金
