树突状细胞瘤苗预防接种联合吉西他滨治疗可提高胰腺癌小鼠模型的生存率  

Preventive Inoculation of DC Vaccine Combined with Gemcitabine Improved the Survival Rate of Pancreatic cancer in mice model

作　　者：汪治宇[1] 王聪敏[1] 王娟[1] 

机构地区：[1]河北医科大学第四医院生物治疗科

出　　处：《药品评价》2012年第18期26-34,共9页Drug Evaluation

摘　　要：目的应用胰腺癌小鼠模型来研究吉西他滨是否可以提高树突状细胞瘤苗接种的疗效。方法 C57B L/6小鼠成功负载经紫外线辐射后的PanO2癌细胞后,从小鼠体内获得骨髓源性DCs然后经皮下给药。预防性接种的小鼠在PanO2癌细胞形成肿瘤威胁前接种瘤苗,每隔一周接种3次,治疗性接种于肿瘤形成可触及结节时开始。吉西他滨经腹腔给药,每周两次。结果预防性DC瘤苗接种可全面阻止皮下及原位肿瘤的发展并且可诱导肿瘤抗原特异性CTLs及免疫记忆。对于已形成皮下肿瘤的模型,治疗性DC瘤苗接种与吉西他滨同样有效(肿瘤威胁形成后58天生存率分别为14%和17%,对照组0%)。以上两种方法联合可显著提高带瘤小鼠的生存率(肿瘤威胁形成后58天生存率为50%)。树突状细胞瘤苗接种也可以预防静脉注射PanO2细胞后肺转移导致的死亡。结论:树突状细胞免疫治疗不仅可以成功地与吉西他滨联合治疗晚期胰腺癌,还能够有效地预防无瘤患者的肿瘤局部复发及转移。Objective To study that if the therapeutic effect of DC vaccine inoculation could be improved by gemcitabine in mice model of pancreatic cancer. Bone marrow-derived DC cells acquired from C57BL/6 mice that load PanO2 cancer cells which already were accepted ultraviolet radiation were administered subcutaneously. Mice of protective inoculation were inoculated before PanO2 cancer cells formed neoplasm,3 times every two weeks. While therapeutic inoculation was performed after the tumor mass could be touch. Mice were administered with gemcitabine intraperitoneal,twice a week. Protective inoculation of DC vaccine could prohibit the tumor progression subcutaneous and in situ,and induce CTLs with tumor specificity and immunologic memory. As for mice with subcutaneous tumor mass,both of therapeutic inoculation and gemcitabine were effective （58 days survival rates after tumor formed were 14% and 17% respectively, while control group was 0%）.The combination of two methods above could notably improve the survival rate of mice with tumor （58 days survival rate after tumor formed was 50%）. DC vaccine also prevented death caused by lung metastasis after injected PanO2 cancer cells intravenously. Conclusion Immunotherapy with DC vaccine could not only treat advanced pancreatic cancer combining with gemcitabine but also effectively protect ones without tumor mass from local recurrence and metastasis.

关 键 词：胰腺癌 树突状细胞瘤苗 吉西他滨 生存率 免疫反应 

分 类 号：R735.9[医药卫生—肿瘤] R-332[医药卫生—临床医学]