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本室以往的研究表明,用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(Itn)基因联合体内转染,具有显著的抗肿瘤效应.本文对其免疫机理进行了进一步研究,发现CT26结肠腺癌细胞体外经过CD/Ltn基因转染并给予前体药物5-FC后,CT26结肠腺癌细胞表达CD80和CD54分子明显增加,提示经CD自杀基因和Ltn基因联转移后,肿瘤细胞免疫原性增加.荷瘤小鼠体内经联合治疗后,小鼠脾细胞分泌IL-2和IFN-γ明显增加.体内用抗CD4、CD8抗体阻断实验研究结果的表明,联合应用自杀基因和Ltn基因治疗主要通过诱导CD8~+ T细胞发挥抗肿瘤作用.
Previous studies in this laboratory have shown that the use of adenovirus as a vector to transfect E. coli cytosine deaminase (CD) gene and mouse lymphocyte chemokine (Itn) gene in vivo has a significant anti-tumor effect. The immunological mechanism was further studied. It was found that when CT26 colon adenocarcinoma cells were transfected with CD/Ltn gene and administered 5-FC as a prodrug in vitro, CT26 colon adenocarcinoma cells showed a significant increase in the expression of CD80 and CD54 molecules, suggesting CD-suicide genes After Lttn gene transfer, the immunogenicity of tumor cells increased. After combined treatment in tumor-bearing mice, IL-2 and IFN-γ secreted by spleen cells of mice were significantly increased. In vivo experiments with anti-CD4 and CD8 antibodies were blocked. The results showed that the combined application of suicide gene and Ltn gene therapy mainly through the induction of CD8 ~ + T cells play an anti-tumor effect.