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本研究以腺病毒作为载体,将大肠杆菌胞嘧啶脱氨酶(CD)基因与小鼠淋巴细胞趋化因子(Ltn)基因体内联合转染,观察了其抗肿瘤效应并分析了免疫机理.小鼠皮下接种结肠腺癌CT26细胞后3天,肿瘤局部注射表达Ltn的重组腺病毒AdLtn和表达CD的重组腺病毒AdCD,然后连续10天给予5一氟胞嘧啶(5-FC)300mg/kg进行治疗,结果表明,联合治疗组荷瘤小鼠皮下肿瘤结节的生长受到明显抑制,小鼠存活期明显长于单用AdLtn治疗组或单用AdCD/5-FC治疗组.经联合治疗后小鼠脾细胞的NK活性和对(37结肠腺癌细胞的CTL杀伤活性明显增强.瘤体细胞FACS分析结果表明,经联合基因治疗后,肿瘤组织CD4~+、CD8~+细胞浸润增加,结肠腺癌细胞表达H-2Kd和B7-1分子明显增加.提示经CD自杀基因和Ltn基因联合治疗后,肿瘤细胞免疫原性增加.本研究结果表明联合应用自杀基因和Ltn基因治疗可以提高机体对肿瘤细胞免疫的应答,增加机体的抗肿瘤作用,是肿瘤基因治疗中一条新的途径.
In this study, adenovirus was used as a vector, and the cytosine deaminase (CD) gene of E. coli was transfected with mouse lymphocytic chemokine (Ltn) gene in vivo. The antitumor effect was observed and the immune mechanism was analyzed. Three days after subcutaneous inoculation of colon adenocarcinoma CT26 cells, the tumor was injected with the recombinant adenovirus AdLtn expressing Ltn and the recombinant adenovirus AdCD expressing CD, and then given 5-fluorocytosine (5-FC) 300 mg/kg for 10 consecutive days. Treatment showed that the growth of subcutaneous tumor nodules was significantly inhibited in the tumor-bearing mice of the combination treatment group. The survival time of the mice was significantly longer than that of the AdLtn alone or AdCD/5-FC alone group. NK activity in spleen cells and the killing activity of CTL in colonic adenocarcinoma cells were significantly enhanced. FACS analysis of tumor cells showed that after combined gene therapy, the infiltration of CD4~+ and CD8~+ cells in tumor tissues increased, and colon adenocarcinoma The expression of H-2Kd and B7-1 molecules in the cells was significantly increased. It was suggested that the immunogenicity of tumor cells was increased after combined treatment of CD suicide gene and Ltn gene. The results of this study suggest that the combination of suicide gene and Ltn gene therapy can improve the body’s tumor cells. Immune A, increase the body’s anti-tumor effect, the tumor gene therapy in a new way.