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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
【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.
【Key words】 Dendritic cell; IFN-γ; Prostatic carcinoma; Immunotherapy;
- 【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