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白细胞介素-18基因与肿瘤细胞裂解物修饰的树突状细胞疫苗对胰腺癌小鼠的免疫治疗作用

The immunotherapeutic effect of dendritic cells vaccine modified with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma.

作者信息

Tang Zhao-Hui, Qiu Wen-Hong, Wu Gao-Song, Yang Xiang-Ping, Zou Sheng-Quan, Qiu Fa-Zu

机构信息

Department of General Surgery of Tong Ji Hospital, Wuhan 430030, Hubei Province, China.

出版信息

World J Gastroenterol. 2002 Oct;8(5):908-12. doi: 10.3748/wjg.v8.i5.908.

Abstract

AIM

To estimate the effect of a therapeutic vaccine against pancreatic carcinoma based on dendritic cell (DC) vaccine modified with tumor lysate and Interleukin-18 gene.

METHODS

The BALB/C mice model of pancreatic carcinoma was induced with DMBA. DC vaccine was constructed through pulsed with tumor lysate and transfected by the recombinant adenoviral vector encoding IL-18 gene. The immunotherapeutic effects of DC vaccine on mice with pancreatic carcinoma were assessed (divided into DC-IL18-Lysate group, DC-Lysate group, DC-IL18 group, DC group, PBS group).

RESULTS

After vaccination of the DC vaccine, the concentration of IL-18 and IFN-gamma were 2161+/-439 ng x L(-1) and 435+/-72 ng x L(-1) in DC-IL18-Lysate group and there was significant difference compared with other groups (P<0.01). After vaccination of the DC vaccine, the transplanted tumors were observed on 30 days in DC-Lysate groups, on 16 days in DC-IL18 groups, on 3 days in control group, but mice remained tumor-free for at least 50 days in DC-IL18-Lysate group and there was significant difference between DC-IL18-Lysate group and other groups (P<0.01). The median survival exceeds 62 days in DC-IL18-Lysate group. But the median survival was 48.6 days in DC-Lysate group, 33 days in DC-IL18 group, 17 days in PBS group. The survival period was obviously prolonged in DC-IL18-Lysate group than in other groups (P<0.05, P<0.01). The weight of pancreatic tumor was 0.22+/-0.083 g in DC-IL18-Lysate group, 1.45+/-0.74 g in DC-Lysate group, 1.89+/-1.34 g in DC-IL18 group, 3.0+/-1.6 g in DC group, 2.9+/-2.0 g in PBS group and the weight of tumor obviously reduced in DC-IL18-Lysate group than in other groups (P<0.05, P<0.01).

CONCLUSION

DC vaccine modified with tumor lysate and Interleukin-18 gene can induce a specific and effective immune response against pancreatic carcinoma cell.

摘要

目的

评估一种基于用肿瘤裂解物和白细胞介素-18基因修饰的树突状细胞(DC)疫苗对胰腺癌的治疗效果。

方法

用二甲基苯并蒽(DMBA)诱导建立BALB/C小鼠胰腺癌模型。通过用肿瘤裂解物脉冲并经编码IL-18基因的重组腺病毒载体转染构建DC疫苗。评估DC疫苗对胰腺癌小鼠的免疫治疗效果(分为DC-IL18-裂解物组、DC-裂解物组、DC-IL18组、DC组、PBS组)。

结果

接种DC疫苗后,DC-IL18-裂解物组中IL-18和IFN-γ的浓度分别为2161±439 ng·L⁻¹和435±72 ng·L⁻¹,与其他组相比有显著差异(P<0.01)。接种DC疫苗后,DC-裂解物组在30天观察到移植瘤,DC-IL18组在16天观察到移植瘤,对照组在3天观察到移植瘤,但DC-IL18-裂解物组小鼠至少50天无瘤,DC-IL18-裂解物组与其他组之间有显著差异(P<0.01)。DC-IL18-裂解物组的中位生存期超过62天。但DC-裂解物组的中位生存期为48.6天,DC-IL18组为33天,PBS组为17天。DC-IL18-裂解物组的生存期明显长于其他组(P<0.05,P<0.01)。DC-IL18-裂解物组胰腺肿瘤重量为0.22±0.083 g,DC-裂解物组为1.45±0.74 g,DC-IL18组为1.89±1.34 g,DC组为3.0±1.6 g,PBS组为2.9±2.0 g,DC-IL18-裂解物组的肿瘤重量明显低于其他组(P<0.05,P<0.01)。

结论

用肿瘤裂解物和白细胞介素-18基因修饰的DC疫苗可诱导针对胰腺癌细胞的特异性有效免疫反应。

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