中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2014年
1期
77-80
,共4页
刘扬%王跃如%王龙%周波%宋振顺%张柏和%吴孟超%Lisa H.Butterfield
劉颺%王躍如%王龍%週波%宋振順%張柏和%吳孟超%Lisa H.Butterfield
류양%왕약여%왕룡%주파%송진순%장백화%오맹초%Lisa H.Butterfield
癌,肝细胞%甲胎蛋白%树突状细胞
癌,肝細胞%甲胎蛋白%樹突狀細胞
암,간세포%갑태단백%수돌상세포
Carcinoma,hepatocellular%Alpha-fetal protein%Dendritic cell
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.
目的 探討甲胎蛋白(AFP)肽片段或Lenti-AFP刺激的樹突狀細胞(DC)製備的肝癌疫苗用于肝癌免疫治療的可行性.方法 採用慢病毒轉染和AFP抗原決定簇肽製備的肝癌疫苗對4組荷瘤裸鼠(Lenti-AFP、AFP1、AFP542組及對照組)進行瞭體內腫瘤細胞殺傷實驗,通過測定成瘤大小及相關細胞因子[白細胞介素(IL)-2和-10、榦擾素-γ、腫瘤壞死因子-α、穿孔素、顆粒酶B、Fas配體]的變化,觀察不同治療組對裸鼠皮下成瘤及其噁化的影響.結果 AFP特異性CD8+T淋巴細胞和CD4+T淋巴細胞肝癌疫苗能有效阻止裸鼠皮下腫瘤的生長,治療組(Lenti-AFP、AFP1、AFP542組)腫瘤直徑[分彆為(7.03±2.78)、(11.00±2.57)、(8.87±3.49) cm]低于對照組(F腫瘤直徑=6.13,P<0.01),腫瘤重量[分彆為(0.478±0.225)、(0.398±0.125)、(0.298±0.099)、(0.228±0.132)g],也低于對照組(F腫瘤重量=5.38,P<0.01).各治療組不同程度上調裸鼠血清中IL-2、榦擾素-γ、腫瘤壞死因子-α、穿孔素、顆粒酶B的水平,而對于T淋巴細胞活化的負調控因子IL-10,具有顯著的抑製作用(P<0.05).結論 AFP特異性CD8+ T/CD4+T淋巴細胞疫苗能有效抑製荷人肝癌裸鼠體內腫瘤的生長.
목적 탐토갑태단백(AFP)태편단혹Lenti-AFP자격적수돌상세포(DC)제비적간암역묘용우간암면역치료적가행성.방법 채용만병독전염화AFP항원결정족태제비적간암역묘대4조하류라서(Lenti-AFP、AFP1、AFP542조급대조조)진행료체내종류세포살상실험,통과측정성류대소급상관세포인자[백세포개소(IL)-2화-10、간우소-γ、종류배사인자-α、천공소、과립매B、Fas배체]적변화,관찰불동치료조대라서피하성류급기악화적영향.결과 AFP특이성CD8+T림파세포화CD4+T림파세포간암역묘능유효조지라서피하종류적생장,치료조(Lenti-AFP、AFP1、AFP542조)종류직경[분별위(7.03±2.78)、(11.00±2.57)、(8.87±3.49) cm]저우대조조(F종류직경=6.13,P<0.01),종류중량[분별위(0.478±0.225)、(0.398±0.125)、(0.298±0.099)、(0.228±0.132)g],야저우대조조(F종류중량=5.38,P<0.01).각치료조불동정도상조라서혈청중IL-2、간우소-γ、종류배사인자-α、천공소、과립매B적수평,이대우T림파세포활화적부조공인자IL-10,구유현저적억제작용(P<0.05).결론 AFP특이성CD8+ T/CD4+T림파세포역묘능유효억제하인간암라서체내종류적생장.
Objective 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.