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IL-12基因修饰瘤苗联合CpG-ODN治疗小鼠眼内黑色素瘤的研究 被引量:1

Study on treating intraocular melanoma in mice with IL-12 gene modified tumor cell vaccine combinated with CpG-ODN
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摘要 目的:观察白细胞介素-12(Interleukin-12,IL-12)基因修饰瘤苗联合含非甲基化的胞嘧啶鸟嘌呤二核苷酸(CpG)基序的寡脱氧核苷酸(oligodeoxynucletide,ODN)即CpG-ODN治疗小鼠眼内黑色素瘤的疗效。方法:将荷瘤模型鼠分为磷酸盐缓冲液(phosphate-buffered saline,PBS)治疗组,IL-12基因修饰肿瘤细胞疫苗(gene modified tumor cell vaccine,GTV)治疗组及GTV联合CpG-ODN(GTVC)治疗组;鼠荷瘤模型建立后的第3d及第10d分别在各组鼠结膜下注射30μLPBS,30μL(3.0×106个细胞)灭活的GTV及含20μgCpG-ODN灭活的GTV,进行角膜溃破时间、淋巴结和肺部转移瘤发生率、生存时间及外周血CD4+和CD8+T细胞比例的观测。结果:GTV组及GTVC组角膜溃破晚于PBS组时间,前两组间差异无统计学意义;鼠荷瘤模型建立后的第18d,GTV组及GTVC组颈部淋巴结转移瘤发生率低于PBS组,前两组组间差异无统计学意义;鼠荷瘤模型建立后的第28d,GTVC组鼠肺转移瘤发生率低于PBS组及GTV组,后两组组间差异无统计学意义;PBS组及GTV组的外周血中CD4+与CD8+T细胞比值下降,GTVC组与阴性对照组组间差异无统计学意义;GTVC组小鼠生存时间长于另两组。结论:新型免疫佐剂CpG-ODN可增强IL-12基因修饰瘤苗的抗眼内黑色素瘤效应。 AIM: To observe the therapeutic effect of interleukin-12 (IL-12) gene modified tumor cell vaccine combinated with CpG oligodeoxynucleotide ( CpG-ODN ) on intraocular melanoma. METHODS: Model mice bearing tumor were divided into 3 groups, respectively phosphate-buffered saline (PBS) treatment group, IL-12 gene modified tumor cell vaccine (GTV) treatment group and GTV combinated with CpG-ODN (GTVC) treatment group. 30mL PBS, 30mL(3.0 × 10^6 cells)inactivated GTV and GTVC containing 20mg CpGODN were respectively injected into subconjunctiva of mice bearing tumor 3 days and 10 days after bearing tumor mouse model had been established. The time of cornea diabrosis, metastases into cervical lymph nodes and lung, survival time and ratio of CD4^+ and CD8^+ T cells in peripheral blood were observed. RESULTS: The time of cornea diabrosis in GTVC group or GTV group was later than that in PBS group, but no statistical difference between GTVC group and GTV group. Metastatic incidence in cervical lymph nodes of GTVC group mice or GTV group mice was lower than that in PBS group 18 days after the model had been established. There was no statistical difference in metastatic incidence between GTV group and GTVC group. Metastatic incidence in lungs of GTVC group mice was lower than that in PBS group or in GTV group 28 days after the model had been established. There was statistical difference in metastatic incidence respectively between PBS group and GTV group. Compared with negative control (NC) group, the ratio of CD4^+ and CD8^+ T cells in peripheral blood was lower in PBS group and GTV group. There was no statistical difference on the ratio between GTVC group and NC group. The survival time in GTVC group was longer than that in PBS group and GTV group, but no difference between PBS group and GTV group. CONCLUSION: CpG-ODN can enhance the therapeutic effect of IL-12 gene modified tumor cell vaccine on intraocular melanoma.
出处 《国际眼科杂志》 CAS 2009年第6期1066-1068,共3页 International Eye Science
基金 中国广东省自然科学基金资助项目(No.5300864)~~
关键词 白细胞介素12 基因修饰瘤苗 胞嘧啶鸟嘌呤寡脱氧核苷酸 眼内黑色素瘤 免疫治疗 Interleukin 12 gene modified tumor vaccine CpG-ODN intraocular melanoma immunotherapy
作者简介 通讯作者:赵军,副主任医师,医学博士。doctorzhaojun@163.com
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