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研究将对巨噬细胞双重功能均具有激活作用的细胞因子GM-CSF的基因转染小鼠腹腔巨噬细胞,再经肿瘤抗原致敏后通过静脉注射用于实验性CT26结肠癌肺转移小鼠的治疗.结果表明,腺病毒介导的GM-CSF基因转染小鼠腹腔巨噬细胞在转染后4h即可分泌较高水平的GM-CSF.转染后10d仍可有效表达;转染后16h左右小鼠腹腔巨噬细胞MHCⅡ类分子的表达明显增强,其抗原提呈能力也达最高水平;对肿瘤细胞的杀伤活性显著增高;荷瘤3d的实验性CT26结肠癌肺转移小鼠经肿瘤抗原致敏的GM-CSF基因转染巨噬细胞治疗后第16天肺部转移结节数明显减少;经治疗小鼠脾细胞经诱导的CTL杀伤活性也明显升高.以上结果提示,GM-CSF基因转染及表达能有效增强小鼠腹腔巨噬细胞的抗原提呈能力及效应功能;经肿瘤抗原刺激后其对转移性肿瘤也有明显的治疗作用.
To study the effect of GM-CSF, a cytokine that activates dual functions of macrophages, transfected into mouse peritoneal macrophages, followed by sensitization with tumor antigens and intravenous injection for experimental CT26 colon cancer lung metastasis in mice. The results showed that adenovirus-mediated transfection of GM-CSF gene into mouse peritoneal macrophages secreted higher levels of GM-CSF 4 h after transfection. Transfection can still be efficiently performed 10 days after transfection. After about 16 hours, the expression of MHC class II molecules in mouse peritoneal macrophages was significantly enhanced, the ability of antigen presentation was the highest, and the cytotoxic activity against tumor cells was significantly higher. The mice with tumor-bearing lung metastases on CT26 for 3 days were significantly improved. Tumor antigen-sensitized GM-CSF gene transfected macrophages significantly reduced the number of metastatic lung nodules on the 16th day after treatment, and the CTL killing activity of the treated mouse spleen cells also increased significantly. The above results suggest that GM - CSF gene transfection and expression can effectively enhance the antigen presentation ability and effector function of mouse peritoneal macrophages. After being stimulated by tumor antigen, it also has obvious therapeutic effect on metastatic tumors.