端粒酶冲击树突状细胞诱导抗前列腺癌免疫  

Telomerase pulsed dendritic cells induced antitumor immune response against prostate cancer in vitro

作　　者：屈艺[1] 张林[1] 黄翔[1] 李虹[1] 吴霞[1] 刘菽秋[1] 

机构地区：[1]四川大学基础与法医学院生物化学与分子生物实验室,成都610041

出　　处：《肿瘤》2006年第3期276-278,281,共4页Tumor

基　　金：四川省科技攻关项目(编号:04SG022-009-2);四川省青年科技基金项目(编号:04ZQ026-027)

摘　　要：目的:探讨端粒酶抗原冲击的树突状细胞(DCs)在体外诱导抗前列腺癌的免疫效应。方法:细胞因子IL-4和GMCSF诱导前列腺癌患者外周血单核细胞(peripheral blood mononuclear cells,PBMC)生成DCs,将端粒酶逆转录酶(humantelomerase reverse transcriptase,hTERT)mRNA转染DCs使之表达hTERT蛋白,诱导产生肿瘤特异性细胞毒性T细胞(cy-totoxic T lymphocyte,CTL)。MTT法检测负载端粒酶抗原的DCs对T细胞的激发效率,LDH法检测激发产生的CTL对前列腺癌细胞的特异性杀伤作用。结果:端粒酶抗原冲击的DCs较非端粒酶冲击的DCs更能有效诱导T细胞增殖(平均刺激增殖指数分别为10.03±0.88和3.95±0.46,P<0.05),经其诱导产生的T细胞对自体肿瘤细胞的特异性杀伤活性明显高于非端粒酶冲击组[平均肿瘤细胞清除率分别为(62.58±9.44)%和(17.67±3.02)%,P<0.05]。结论:端粒酶抗原冲击的DCs可望成为前列腺癌肿瘤疫苗,在前列腺癌免疫治疗中发挥作用。Objective：To study whether telomerase pulsed dendritic cells （DCs） could induce antitumor immune response against prostate cancer in vitro. Methods： DCs isolated from peripheral blood monocytes of prostate cancer patients were stimulated with recombinant human interleukin-4 （IL-4） and recombinant human granulocyte macrophage colony stimulating factor （GM-CSF）. Then these DCs were transfected with human telomerase reverse transcriptase （hTERT） mRNA and co-cultured with autologous T cells to induce cytotoxic T lymphocytes （CTL）. The proliferation of T cells stimulated by DCs was determined by MTT assay;the tumor clearance by the CTL was detected by LDH method. Results：The stimulation index of T lymphocyte proliferation induced by telomerase pulsed DCs was significantly higher than those not pulsed by telomerase （10.03 ±0.88 vs 3.95±0.46, P〈0.05）. The CTL cells activated by telomerase pulsed DCs had greater tumor clearance capability than those activated by DCs not pulsed by telomerase （tumor clearance ratio ; 62.58%± 9.44% vs 17.67%±3.02 %, P〈0.05 ）. Conclusion： Telomerase pulsed DCs could induce potent antitumor immune activity, and might have potential value in clinical biotherapy for prostate cancer.

关 键 词：前列腺肿瘤 端粒酶 树突细胞 免疫疗法 

分 类 号：R730.3[医药卫生—肿瘤]