IL-12瘤苗与131I-1E2 协同抗瘤作用研究

目的:建立稳定表达IL- 12的小鼠Lewis肺癌瘤苗LLC/mIL-12；评估尾静脉注射131I- 1E2（131I 标记抗肺癌单克隆抗体1E2）抑瘤效果及LLC/mIL-12对131I- 1E2 靶向治疗增效作用。方法:制备LLC/mIL-12；Na131I 标记1E2；建立C57BL/6 小鼠移植瘤模型，比较单纯尾静脉注射131I- 1E2 或联合瘤内注射LLC/mIL-12时131I- 1E2 在小鼠体内分布。成瘤小鼠随机分组，为GT、LLC/mIL-12）、RIT（Radioimmunotherapy，放射免疫治疗）、PBS 和GT+RIT组，治疗后测量肿瘤体积及重量，计算抑瘤率，检测CTL 和NK活性。结果:131I- 1E2 能有效靶向肿瘤组织，尤其联合LLC/mIL-12。与单用GT或RIT 比较，GT+RIT能有效地上调IL- 12表达、抑制肿瘤生长，GT及联合组有大量CD4+、CD8+淋巴细胞浸润，NK和CTL 细胞活性增强。联合组131I- 1E2 更多积聚在肿瘤组织。结论:131I- 1E2 明显抑制肿瘤生长，具有潜在的临床应用价值，有可能成为新的肿瘤靶向治疗药物。 

Synergistic Antitumor Effect of IL-12 Tumor Vaccine and 131I-1E2

Objective: To establish the murine Lewis Lung Carcinoma cell tumor vaccine, LLC/IL- 12, which can stably express the IL- 12(interleukin-12) gene, and to assess the antitumor effect of 131I- 1E2 (anti-lung cancer monoclonal antibody 1E2 labeled with iodine- 131 ) through tail intravenous injection and the synergistic effect of IL-12vaccine on 131I- 1E2 target -ed therapy.Methods:LLC/IL-12tumor vaccine was prepared. Na 131I was used to label 1E2 Mab. The model of C57BL/6 mice-transplanted tumor was established and the distribution of 131I- 1E2 in mice in different groups was observed by tail in -travenous injection of 131I- 1E2 or combined with intratumoral injection LLC/ mIL- 12. When the tumors were large enough, 40 mice were divided into4 groups: (1) GT group (Gene therapy, i.e. LLC/mIL-12), (2) RIT group (Radio immunotherapy), ( 3) PBS group, and ( 4) GT+RIT group. Tumor volume and weight were measured and tumor-inhibitory ratio was calculated af-ter treatment. Analysis of CTL and NK activity was performed. Results: 131I- 1E2 could effectively target tumor tissue, espe -cially when combined with IL-12vaccine. RIT+GT can up-regulate the expression of IL-l2 gene and inhibit the tumor growth compared with GT or RIT alone. There was abundant CD4 + and CD8 + T lymphocyte infiltration in the GT and combined group, and NK and CTL cell activity was improved. There was more 131I- 1E2 accumulated in tumor tissue in the combination group. Conclusion: 131I- 1E2 can obviously inhibit tumor growth and has potential clinical application value.131I- 1E2 may possibly become a new tumor targeting agent.