Tang Zhao-Hui, Qiu Wen-Hong, Wu Gao-Song, Yang Xiang-Ping, Zou Sheng-Quan, Qiu Fa-Zu
Department of General Surgery of Tong Ji Hospital, Wuhan 430030, Hubei Province, China.
World J Gastroenterol. 2002 Oct;8(5):908-12. doi: 10.3748/wjg.v8.i5.908.
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.
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).
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).
DC vaccine modified with tumor lysate and Interleukin-18 gene can induce a specific and effective immune response against pancreatic carcinoma cell.
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。
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)。
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)。
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。