HLA-restricted presentation of WT1 tumor antigen in B-lymphoblastoid cell lines established using a maxi-EBV system
HLA-restricted presentation of WT1 tumor antigen in B-lymphoblastoid cell lines established using a maxi-EBV system
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DOI：
10.1038/cgt.2012.34
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发表时间：
2012-08-01
影响因子：
6.4
通讯作者：
Tsurumi, T.
中科院分区：
文献类型：
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作者：
Kanda, T.;Ochi, T.;Tsurumi, T.
类淋巴母细胞系 (LCL) 是通过用 Epstein-Barr 病毒 (EBV) 体外感染外周 B 淋巴细胞而建立的，是有效的抗原呈递细胞。然而，LCL 呈递转导的肿瘤抗原的能力尚未得到详细评估。我们报告了一种单步策略，利用重组 EBV (maxi-EBV) 将任何个体的 B 淋巴细胞转化为表达目的转基因的无限生长的 LCL。该策略已成功用于建立表达 Wilms 肿瘤基因 1 (WT1) 肿瘤抗原 (WT1-LCLs) 的 LCL，这是癌症免疫治疗的一个有吸引力的靶点。建立的 WT1-LCL 比 K562 白血病细胞表达更丰富的 WT1 蛋白，已知 K562 白血病细胞过度表达 WT1。 WT1特异性细胞毒性T淋巴细胞系以人类白细胞抗原限制的方式有效裂解WT1-LCL，但裂解不表达WT1的对照LCL效果较差。这些结果表明转导的 WT1 抗原被加工并呈递在 WT1-LCL 上。该实验策略可用于建立表达其他肿瘤抗原的LCL，并将在癌症免疫治疗领域找到广泛的应用。
Lymphoblastoid cell lines (LCLs), which are established by in vitro infection of peripheral B-lymphocytes with Epstein-Barr virus (EBV), are effective antigen-presenting cells. However, the ability of LCLs to present transduced tumor antigens has not yet been evaluated in detail. We report a single-step strategy utilizing a recombinant EBV (maxi-EBV) to convert B-lymphocytes from any individuals into indefinitely growing LCLs expressing a transgene of interest. The strategy was successfully used to establish LCLs expressing Wilms' tumor gene 1 (WT1) tumor antigen (WT1-LCLs), which is an attractive target for cancer immunotherapy. The established WT1-LCLs expressed more abundant WT1 protein than K562 leukemic cells, which are known to overexpress WT1. A WT1-specific cytotoxic T lymphocyte line efficiently lysed the WT1-LCL in a human leukocyte antigen-restricted manner, but poorly lysed control LCL not expressing WT1. These results indicate that the transduced WT1 antigen is processed and presented on the WT1-LCL. This experimental strategy can be applied to establish LCLs expressing other tumor antigens and will find a broad range of applications in the field of cancer immunotherapy.