DC融合瘤苗治疗大鼠腹腔播散性卵巢癌  

Immunotherapy of intraperitoneal disseminated ovarian cancer in rats using dendritic cell-tumor fusion vaccine

作　　者：康玉[1] 徐丛剑[1] 刘惜时[1] 吴超群[2] 钟翠平[3] 顾健人[4] 

机构地区：[1]复旦大学附属妇产科医院,上海200011 [2]复旦大学遗传工程国家重点实验室 [3]复旦大学上海医学院组胚解剖系 [4]上海市肿瘤研究所癌基因及相关国家重点实验室

出　　处：《现代妇产科进展》2005年第4期266-269,共4页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目(30070783);上海市重大科技攻关项目(03DZ19234)

摘　　要：目的:研究树突状细胞(DC)与卵巢癌融合的融合瘤苗对大鼠腹腔播散性卵巢癌的治疗作用,并观察其体内应用的安全性。方法:用聚乙二醇法将Fischer344(F344)大鼠骨髓来源的DC与卵巢癌上皮细胞株NuTu19细胞在体外融合制备融合瘤苗(DCNuTu19)。流式细胞术检测DCNuTu19的免疫相关表型。将DCNuTu19接种于F344大鼠皮下,观察它在体内的成瘤性。用乳酸脱氢酶释放法检测经过DCNuTu19免疫的大鼠脾细胞毒性T淋巴细胞(CTL)对NuTu19细胞的杀伤作用。复制腹腔播散性卵巢癌的F344大鼠模型,观察DCNuTu19对它的治疗作用。结果:DCNuTu19高表达主要组织相容性复合物II(MHCII)分子OX6、共刺激分子B72、细胞间粘附分子ICAM1和大鼠DC的标志性抗原整合素OX62。与NuTu19相比,DCNuTu19在大鼠体内成瘤率降低,成瘤时间延迟,两组平均瘤重具有统计学差异(P<0.05)。经DCNuTu19免疫的大鼠脾CTL对NuTu19细胞的杀伤活性显著增高(P<0.01)。与对照组相比,经DCNuTu19治疗后大鼠的病情发展速度减缓,生存期明显延长(P<0.01)。结论:卵巢癌DC融合瘤苗能显著提高大鼠CTL杀伤活性,诱导高效而特异的抗卵巢癌免疫效应,延长患有腹腔播散性卵巢癌大鼠的生存时间。Objective：To study the therapeutic efficacy and safety of immunotherapy with dendritic cell （DC）-tumor fusion vaccine on intraperitoneal disseminated ovarian carcinoma in rats.Methods： DCs derived from rat bone marrow of Fischer344（F344） were fused with ovarian tumor cell line NuTu-19 using polyethylene glycol （PEG）.The expression of the surface markers on the DC-tumor fusion vaccine （DC-NuTu-19） was analyzed by flow cytometry.After DC-NuTu-19 was subcutaneously injected to the right midflank of F344 rats,the tumorigenicity was observed in vivo.Cytotoxic T lymphocyte （CTL） activity from the spleen T lymphocyte cells of vaccine-treated rats was then examined using LDH cytotoxicity assays.Rats were then intraperitoneally injected with 5×10^6 NuTu-19 cells,followed by treatment of DC-NuTu-19 on days 7 and 14.The rats＇survival time was recorded and statistically analyzed. Results： DC-Nu-Tu-19 highly expressed MHC Ⅱ antigens （OX6）, costimulatory molecules （B7-2）, integrin （OX62） ,and adhesion molecules （ICAM-1）.Tumor incidence and tumor weight were reduced in rats inoculated with DC-NUTU-19,compared with rats inoculated with NuTu-19 （P〈0.05）.The spleen CTL activity against NuTu-19 cells in rats vaccined with DC-NuTu-19 was significantly higher than that of the control groups （P〈0.01）.Immunization of F344 rats with DC-NuTu-19 induced more potent immunotherapeutic effect against parental tumor cells challenge and prolonged survival time than the control groups （P〈0.01）.Conclusion：Efficacy of immunotherapy with DC-tumor fusion vaccine is confirmed in rats with intraperitoneal disseminated ovarian carcinoma by this study.

关 键 词：卵巢肿瘤 树突细胞 融合细胞 癌症疫苗 

分 类 号：R737.31[医药卫生—肿瘤]