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转染干扰素-γ诱导蛋白-10基因构建树突状细胞前列腺癌瘤苗及其抗肿瘤免疫作用的检测

The immunotherapeutic effect of dendritic cells vaccine modified with IFN-γ inducible protein-10 gene and tumor cell lysate on mice with prostate cancer

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【作者】 李博唐孝达夏术阶徐东亮张新华鲁军吴超群钟翠平

【Author】 LI Bo;TANG Xiao-da;XIA Shu-jie, et al. Department of Urology, The First People’s Hospital of Shanghai, Shanghai 200080, China

【机构】 上海市第一人民医院泌尿外科复旦大学上海医学院解剖组织胚胎系复旦大学遗传研究所复旦大学上海医学院解剖组织胚胎系 200080200080200080

【摘要】 目的 将小鼠前列腺癌细胞株RM-1裂解产物加载树突状细胞(DC)后,转染干扰素-γ诱导蛋白-10(IP-10)基因构建DC瘤苗,探讨该瘤苗对小鼠抗肿瘤免疫反应的诱导作用。方法将RM-1细胞的裂解产物作为肿瘤抗原加载小鼠骨髓来源的DC,并通过脂质体法转染IP-10基因,构建DC瘤苗;检测DC瘤苗的抗前列腺癌免疫治疗作用和免疫保护作用。结果 转染DC强表达IP-10,其上清对淋巴细胞有较强的趋化作用;构建的DC瘤苗能诱导特异性抗前列腺癌免疫反应,经瘤苗处理的荷瘤小鼠瘤体生长减慢,存活期延长;瘤苗还具有明显的免疫保护作用。结论构建的前列腺癌DC瘤苗在体内能有效诱导抗肿瘤免疫反应和免疫保护功能。

【Abstract】 Objective To investigate the effect of a therapeutic vaccine against protate cancerbased on dendritic cells (DC) modified with whole tumor lysate (Tuly) and IFN--rinducible protein-10(IP-10) gene. Methods DC were propagated from bone marrow (BM) of C57BL/6 mice in vitro withGM-CSF and IL--4. On day 5 of culture, DC were harvested and incubated with mice prestate cancer cellline RM--1’s whole lysate at a ratio of three tumor cells equivalents to one DC. After 18 h of incubation,DC were transfected with a plasmid vector expressing IP-10 cDNA by DOTAP liposome. The im-munotherapeutic effects of DC vaccine on mice with prostate cancer were assessed. Results The IP-10plasmid vector was successfully transfected into DC and the DC tranfected with IP-10 gene could synthe-size and secrete IP-10 chemokine, which could increase the preferential chemotaxis of DC to T cells. Inthe C57BL/6 mice model with the pre--established subcutaneous RM--1 prosate cancer, immunization ofDC vaccine modified with Tuly and IP--10 (IP-10/Tuly-DC) inhibited the tumor growth most signifi-cantly when compared with IP10-DC, Tuly-DC, pcDNA3. 1--DC, DC or PBS counterparts (P < 0. 01) andthe survival time of the mice treated with IP-10/Tuly-DC was also greatly extended (P < 0. 01). The IP-10/Tuly-DC immunized mice also exhibited resistance to tumor challenge most effectively (P < 0. 05).Conclusion DC vaccine modified with whole tumor lysate and IP-10 gene might elicit significant antitu-mor effects through efficient induction of antitumor immunity and might be of therapeutic potentials forprostate cancer.

  • 【文献出处】 中华实验外科杂志 ,Chinese Journal of Experimental Surgery , 编辑部邮箱 ,2003年12期
  • 【分类号】R737.25
  • 【被引频次】4
  • 【下载频次】108
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