摘要目的 探讨甲胎蛋白(AFP)肽片段或Lenti-AFP刺激的树突状细胞(DC)制备的肝癌疫苗用于肝癌免疫治疗的可行性.方法 采用慢病毒转染和AFP抗原决定簇肽制备的肝癌疫苗对4组荷瘤裸鼠(Lenti-AFP、AFP1、AFP542组及对照组)进行了体内肿瘤细胞杀伤实验,通过测定成瘤大小及相关细胞因子[白细胞介素(IL)-2和-10、干扰素-γ、肿瘤坏死因子-α、穿孔素、颗粒酶B、Fas配体]的变化,观察不同治疗组对裸鼠皮下成瘤及其恶化的影响.结果 AFP特异性CD8+T淋巴细胞和CD4+T淋巴细胞肝癌疫苗能有效阻止裸鼠皮下肿瘤的生长,治疗组(Lenti-AFP、AFP1、AFP542组)肿瘤直径[分别为(7.03±2.78)、(11.00±2.57)、(8.87±3.49) cm]低于对照组(F肿瘤直径=6.13,P＜0.01),肿瘤重量[分别为(0.478±0.225)、(0.398±0.125)、(0.298±0.099)、(0.228±0.132)g],也低于对照组(F肿瘤重量=5.38,P＜0.01).各治疗组不同程度上调裸鼠血清中IL-2、干扰素-γ、肿瘤坏死因子-α、穿孔素、颗粒酶B的水平,而对于T淋巴细胞活化的负调控因子IL-10,具有显著的抑制作用(P＜0.05).结论 AFP特异性CD8+ T/CD4+T淋巴细胞疫苗能有效抑制荷人肝癌裸鼠体内肿瘤的生长.

abstractsObjective To study the posibility of hepatocellular carcinoma HCC) vaccines from dendritic cells (DCs) stimulated with alpha fetal protein (AFP) peptides or Lenti-AFP for hepatoceHular carcinoma (HCC) immunotherapy.Methods We created a lentivirus expressing AFP (Lenti-AFP) and AFP peptides liver tumor vaccines,and antitumor activity of AFP-specific HCC vaccines for tumor growth and related cytokines [interleukin (IL)-2,interferon (IFN)-γ,IL-10,tumor necrosis factor (TNF)-αt,perforin and granzyme B,FasL) were observed in 4 groups (Lenti-AFP,AFP1,AFP542 and control) in vivo.Results The AFP-specific tumor vaccines could efficiently kill HCC cells in vivo.The tumor diameter in control group was (12.28 ±3.49) cm,and that in treatment groups was (7.03 ±2.78),(11.00 ±2.57),(8.87 ±3.49) cm,respectively (FD =6.13,P＜0.01).The tumor weight in control group was (0.478 ± 0.225) g,and that in treatment groups was (0.398 ± 0.125),(0.298 ± 0.099),(0.228 ±0.132) g respectively (Fw =5.38,P ＜ 0.01).The levels of IL-2,IFN-γ,TNF-α,perforin and granzyme B were increased to varying degrees,and those of IL-10 were significantly reduced in the treatment groups (P ＜0.05).Conclusion AFP-specific CD8 +/CD4 + T cells tumor vaccines which were activated by either Lenti-AFP-engineered or AFP peptide-pulsed DCs have obviously antitumor activity in vivo.This study provides new insight into the design of HCC immunotherapy.