K-ras(12-Val)树突状细胞疫苗诱导抗胰腺癌免疫反应  

Immunotherapy Research on Pancreatic Cancer Induced by Dendritic Cells Pulsed with Mutant K-ras Peptide(12-Val)

作　　者：杨波[1] 何杨[2] 孙冬林[1] 邹岩[1] 秦锡虎[1] 黄伯华[1] 吴翼伟[3] 

机构地区：[1]苏州大学附属第三医院肝胆外科,江苏常州213003 [2]苏州大学附属第一医院江苏省血液研究所,江苏苏州215006 [3]苏州大学附属第一医院核医学科,江苏苏州215006

出　　处：《苏州大学学报（医学版）》2007年第5期691-693,700,共4页Suzhou University Journal of Medical Science

基　　金：江苏省社会发展计划资助项目(BS2004016)

摘　　要：目的探讨构建K-ras(12-Val)树突状细胞(DC)疫苗体外诱导抗胰腺癌特异性免疫反应的可行性。方法采用健康人外周人单核细胞(PBMC)体外刺激分化的DC,负载K-ras(12-Val)多肽后诱导成熟,流式细胞仪测定其细胞表型;与PBMC混合培养扩增特异性细胞毒性T淋巴细胞(CTL),MTT法测定CTL对胰腺癌细胞和正常细胞的免疫杀伤活性。结果负载K-ras(12-Val)多肽的DC成熟后能较好表达突变位点并能有效地刺激T淋巴细胞活化,其诱导产生的CTL对表达该突变的胰腺癌细胞有较好的免疫杀伤作用,对正常组织无损伤作用。结论利用K-ras(12-Val)DC疫苗能成功诱导出较强的抗胰腺癌免疫反应,且具有高度特异性。Objective To study if dendritic cell pulsed with mutant K-ras peptide（12-Val） can activate efficient specific anti-tumor immune response on pancreatic cancer. Methods Immature dendritic cell were pulsed with synthesized mutated peptide. When it was matured,the expression rate of K-ras antigen epitope was speculated on DC surface by monoantibody（K-ras-12Val）. ^3H-thymidine incorporation test was used to detect the proliferation and activation of CTL stimulated by DCs in virto. The killing effects of CTL on pancreatic cancer and nomal tissue were also observed and assessed by MTT method. Results The mutation epitope induced by mutated peptide was able to be presented on the dendritic cell＇s surface efficiently.DC vaccine was able to activate homologous and own T cell. The activated CTL was able to kill the tumor cell efficiently without damage the nomal tissue. Conclusion K-ras （12-Val） DC vaccine can induce specific immunity against pancreatic cancer strongly.

关 键 词：K-ras多肽 树突状细胞 胰腺癌 免疫治疗 

分 类 号：R735.903[医药卫生—肿瘤]