白细胞介素-18与癌细胞裂解物修饰的树突状细胞疫苗对胰腺癌的免疫治疗作用

Immunotherapeutic efficacy of dendritic cells vaccine modified with interleukin-18 and tumor cell lysates in mice with pancreatic carcinoma

目的 观察经白细胞介素 18(IL 18)和胰腺癌细胞裂解物修饰的树突状细胞 (DC)疫苗对胰腺癌荷瘤小鼠的免疫治疗作用。方法 用药物诱导制成BALB/c小鼠的胰腺癌模型。通过IL 18和癌细胞裂解物修饰小鼠DC(MTSC4) ,制成DC疫苗 ,检测各组血清中细胞因子IL 18、干扰素γ(IFN γ)的浓度 (分为DC IL18 裂解物组 ,DC 裂解物组 ,DC IL 18组 ,DC组 ,PBS组 ) ,研究了其对小鼠胰腺癌的免疫治疗作用。结果 DC IL18 裂解物组中IL 18与IFN γ的浓度 ( 2 161± 43 9)μg/L和 ( 4 3 5± 72 ) μg/L ,与其余各组比较差异有显著性 (P <0 .0 5 ,P <0 .0 1)。DC IL18 裂解物组接种胰腺癌细胞后 5 0d均未见移植肿瘤形成 ,与其余各组比较差异有非常显著性 (P <0 .0 1)。对胰腺癌细胞的细胞毒作用以DC IL18 裂解物组最强 ,DC 裂解物组次之 ,DC IL18组较弱 ,其余 2组则缺乏 (P <0 .0 1)。DC IL18 裂解物组的小鼠的生存期比他各组明显延长 ,且肿瘤的重量比其他各组明显减轻 (P <0 .0 1,P <0 .0 5 )。结论 IL 18和胰腺癌细胞裂解物修饰的DC疫苗对胰腺癌荷瘤小鼠有明显的免疫治疗作用。

Objective To observe the immunotherapeutic effects in mice bearing pancreatic carcinoma by dendritic cells vaccine modified with IL-18 and tumor cell lysate.Methods The pancreatic carcinoma was induced in BALB/c mice by DMBA.Dendritic cells (MTSC4) were modified with IL-18 and tumor lysate.The immune preventative and immnotherapeutic effects of DC vaccines in mice with pancreatic carcinoma were assessed (divided into DC-IL18-lysate group,DC-lysate group,DC-IL18 group,DC group,PBS group).Results After the mice immunized for 7 days,the concentrations of IL-18 and IFN-γ were (2?161±439) μg/L and (435±72) μg/L in DC-IL18-lysate group respectively.After vaccination of the DC vaccines,the mice remained tumor-free for at least 50 days in DC-IL18-lysate group.There was significant difference between DC-IL18-lysate group and any other groups (P<0.01).DC-IL18-lysate group showed the strongest cytolytic activity against pancreatic carcinoma cells,followed by DC-lysate group and DC-IL18 group.The survival time was obviously prolonged in DC-IL18-lysate group as compared with any other groups,while the weight of pancreatic tumor was obviously reduced (P<0.05,P<0.01).Conclusion DC vaccine modified with IL-18 and tumor cell lysate can induce a specific and effective immune response against pancreatic carcinoma in mice.