白介素12基因修饰的树突细胞疫苗治疗自发性转移性肺癌

背景与目的:对转移性肺癌的治疗已进行了大量研究,但仍缺乏有效的治疗方法。本研究目的是探讨白介素12(IL-12)基因修饰的树突细胞(DC)疫苗对自发性转移性肺癌的治疗作用。方法:小鼠足垫注射3LLLewis肺癌细胞,建立自发性转移性肺癌模型,经IL-12基因修饰、3LL特异抗原多肽Mut1体外致敏DC疫苗(DC-IL-12/Mut1)皮下免疫2次,观察荷瘤鼠肺重量、肺表面转移结节数量、存活期及相应免疫指标的变化,组间差异行t检验,生存期行时序检验。结果:与对照组(DC-LacZ/Mut1)相比,DC-IL-12/Mut1组肺重量轻、肺表面转移结节数量少、存活期长(P<0.01),细胞毒性T淋巴细胞(CTL)活性和NK活性增强(P<0.01)。结论:IL-12基因修饰的DC疫苗对自发性转移性肺癌有明显的治疗作用,其可能机理是诱导特异性CTL和增强NK活性。

Treatment of spontaneous metastatic lung cancer with interleukin-12 gene-modified dendritic cells vaccine

Background & Objective: Although many works have been done in treatment of metastatic lung cancer, effective method is lacked. This study was designed to investigate the treatment of spontaneous metastatic lung cancer by interleukin 12 ( IL 12) gene modified dendritic cells (DC) vaccine. Methods: The spontaneous metastatic lung cancer model, prepared by injection of the 3LL Lewis lung cancer cells into the footpads of C57BL/6 mice, were treated by subcutaneous vaccination with tumor antigen peptide Mut1 pulsed, IL 12 gene modified dendritic cells (DC IL 12/Mut1)derived from the normal bone morrow. After treatment, the lung weight, the number of lung metastatic nodes, the survival time of the tumor bearing mice were observed, and the NK and CTL activities were respectively determined. Results: Compared with mice treated with Mut1 pulsed, control LacZ gene modified DC and untreated DC, tumor bearing mice treated with DC IL 12/Mut1 had the lightest lung weights (P< 0.01), the least lung metastatic node numbers (P< 0.01), the longest survival time (P< 0.01),also with the induction of potent CTL activity (P< 0.01) and NK activity (P< 0.01). Conclusion:Tumor antigen pulsed, IL 12 gene modified dendritic cells have significant therapeutic effects on the spontaneous metastatic lung cancer, the possible mechanism involved with induction of CTL activity and enhancement of NK activity.