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

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。

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

Objective To investigate the effect of a therapeutic vaccine against protate cancer based 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 with GM-CSF and IL--4. On day 5 of culture, DC were harvested and incubated with mice prestate cancer cell line 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-10 plasmid 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. In the C57BL/6 mice model with the pre--established subcutaneous RM--1 prosate cancer, immunization of DC 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) and the 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 for prostate cancer.