WT1特异性CD8^+T细胞治疗乳腺癌的实验研究  

Experimental study of WT1 specific CD8^+T cells in the treatment of breast cancer

作　　者：王新超[1] 郝素红[1] 高英堂[2] 邱丽君[1] 赵爽[1] 韩璐[1] 

机构地区：[1]天津市第四中心医院,300140 [2]天津市第三中心医院

出　　处：《天津医药》2016年第4期397-400,共4页Tianjin Medical Journal

基　　金：天津市卫生行业重点攻关项目(12KG109)

摘　　要：目的通过检测Wilms’肿瘤基因1(WT1)特异性CD8+T细胞对乳腺癌细胞的杀伤活性,探讨正常外周血中提取的WT1特异性CD8+T细胞用于治疗乳腺癌的可行性。方法运用流式细胞仪检测20例人白细胞抗原(HLA)-A2血清阳性健康志愿者外周血中WT1特异性CD8+T细胞的浓度,通过WT1/主要组织相容性复合体(MHC)连锁状多聚体磁珠分选WT1特异性CD8+T细胞并进行培养,细胞毒性实验检测WT1特异性CD8+T细胞的功能。结果 20例HLA-A2血清阳性健康志愿者外周血中均可检测到WT1特异性CD8+T细胞,12例健康外周血中WT1特异性CD8+T细胞的浓度>0.5%,其中4例>1%。WT1/MHC连锁状多聚体磁珠分选后,其浓度明显增加至80%左右。WT1特异性CD8+T细胞可特异性杀伤WT1多肽负载的乳腺癌细胞株。结论健康志愿者外周血中可检测到WT1特异性CD8+T细胞,该细胞可能对乳腺癌细胞具有特异性杀伤作用,提示WT1特异性CD8+T细胞用于乳腺癌过继性免疫治疗的可能性。Objective To investigate the feasibility of Wilms＇ tumor gene 1（WT1）- specific CD8＋T cells from periph-eral blood for the treatment of breast cancer by detecting the killing activity of WT1 specific CD8＋T cells on breast cancercells. Methods Flow cytometry was used to detect WT1-specific CD8＋T cells in the peripheral blood of 20 samples fromHLA-A2 seropositive healthy donors, which were isolated by WT1/MHC streptamer magnetic beads and cultured. The func-tion of WT1-specific CD8＋T cells were analysis by cytotoxicity assay. Results Twelve of 20 healthy donors had naiveWT1-specific CD8＋T-cell frequencies of 0.5%, and 4 of 20 even 1.0% of all CD8＋T cells. After positive selection bymagnetic cell separation, a purity of up to 80% can be achieved. WT1 specific CD8＋T cells can specifically kill breast can-cer cell line with WT1 polypeptide. Conclusion WT1 specific CD8＋T cells can be detected in peripheral blood of healthyvolunteers. WT1 specific CD8＋T cells have killing effect on breast cancer cells, suggesting the feasibility of adoptive immu-notherapy for breast cancer.

关 键 词：乳腺肿瘤 免疫疗法 过继 CD8阳性T淋巴细胞 WT1 细胞免疫治疗 

分 类 号：R737.9[医药卫生—肿瘤]