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特异性T细胞免疫治疗脑胶质瘤模型的研究

Specific T cell immunotherapy against glioblastoma with mouse model

摘要:

目的 探讨特异性T细胞过继治疗脑胶质瘤的可行性及有效性.方法 将C57BL/6小鼠树突状细胞(DC)与GL261细胞抗原共育,再与T细胞共培养,检测T细胞体外杀伤作用.建立GL261-C57 BL/6小鼠脑胶质瘤模型,随机分两组,治疗组用上述T细胞进行免疫治疗,对照组注射磷酸盐缓冲液(PBS),检测小鼠外周血T细胞亚群,磁共振检测小鼠成瘤情况,观察生存期并解剖死亡小鼠观察成瘤情况.结果 体外实验效靶比为60∶1时,成熟DC组T细胞杀伤率为(62.67±2.52)%,未成熟DC组为(26.33±2.08)% (P =0.000).T细胞治疗后小鼠外周血CD8a/CD4比值为1.18±0.31,对照组为0.28±0.05(P=0.047),治疗组磁共振未见肿瘤生长,对照组生存期为(22.63±2.38)d,治疗组死亡2只,其余均存活至实验结束(80 d)(P =0.001).解剖发现,对照组小鼠均可见肿瘤生长,治疗组在实验结束前死亡的2只可见肿瘤生长,存活至实验结束的小鼠未见肿瘤生长.结论 GL261细胞抗原诱导的特异性T细胞在动物实验中有抑制胶质瘤的作用.

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abstracts:

Objective To investigate the feasibility and effectiveness of specific T cell immunotherapy against glioblastoma in vivo.Methods Total tumor antigen (TTA) was extracted from GL261 cells and to sensitize the dentric cells (DCs) from C57BL/6 mice.T cells were co-cultured with maturated DCs and the cytotoxicity against glioma cells were analyzed.GL261 cells were intracranially implanted into 16 C57BL/6 mice.Eight were intravenously injected with specific T cells and the others were injected with PBS.A consecutive monitor was conducted with MR,and the subpopulation of T lymphocyte from mice blood was analyzed with flow cytometry.Draw the survival curves at the end.Results When the effector-target (E∶T) ratio was 60∶1,the killing rate of effect T cells in matured DC group was (62.67 ± 2.52)%,while the control group was (26.33 ±2.08)% (P=0.000).The ratio of CD8a/CD4 in mice peripheral blood after treated with T cells was 1.18 ±0.31,higher than that of the control group,which was 0.28 ± 0.05 (P =0.047).MRI showed that tumors were significantly inhibited after specific T cell immunotherapy.The survival period of the control group was (22.63 ± 2.38) d,there were 2 mouses died in the treatment group and the rest survived until the end of the experiment (80 d) (P =0.001).Through autopsy,we found that the control group died as tumor growth,and two of the treatment group which dead before the end of the experiment were also found tumor growth,we didn't observe tumor among other mice of treatment group.Conclusion TTA from GL261 could elicit specific adoptive T cell immunotherapy against glioma both in vitro and in vivo.

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作者: 张静文 [1] 杨紫潇 [1] 徐旸 [1] 齐增鑫 [1] 张宏义 [2] 毛颖 [1] 花玮 [1]
期刊: 《中华实验外科杂志》2018年35卷12期 2281-2283页 ISTICPKU
栏目名称: 实验研究
DOI: 10.3760/cma.j.issn.1001-9030.2018.12.032
发布时间: 2019-01-10
基金项目:
国家自然科学基金 国家国际科技合作专项项目 上海市科委科研计划项目(16495800300)National Natural Science Foundation International S&T Cooperation Program of China Shanghai Committee of Science and Technology
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