| Eradication of Hepatocellular Carcinoma by NKG2D-Based CAR-T Cells |
| Sun, B; Yang, D; Dai, HJ; Liu, XY; Jia, R; Cui, XY; Li, WX; Cai, CC; Xu, JM; Zhao, XD
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| 2019
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| 发表期刊 | CANCER IMMUNOLOGY RESEARCH
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| ISSN | 2326-6066
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| 卷号 | 7期号:11页码:1813-1823 |
| 摘要 | Despite the great success of chimeric antigen receptor T (CAR-T)-cell therapy in the treatment of hematologic malignancies, CAR-T-cell therapy is limited in solid tumors, including hepatocellular carcinoma (HCC). NK group 2 member D (NKG2D) ligands (NKG2DL) are generally absent on the surface of normal cells but are overexpressed on malignant cells, offering good targets for CAR-T therapy. Indeed, analysis of The Cancer Genome Atlas and HCC tumor samples showed that the expression of most NKG2DLs was elevated in tumors compared with normal tissues. Thus, we designed a novel NKG2D-based CAR comprising the extracellular domain of human NKG2D, 4-1BB, and CD3 zeta signaling domains (BBz). NKG2D-BBz CAR-T cells efficiently killed the HCC cell lines SMMC-7721 and MHCC97H in vitro, which express high levels of NKG2DLs, whereas they less efficiently killed NKG2DL-silenced SMMC-7721 cells or NKG2DL-negative Hep3B cells. Overexpression of MICA or ULBP2 in Hep3B improved the killing capacity of NKG2D-BBz CAR-T cells. T cells expressing the NKG2D-BBz CAR effectively eradicated SMMC-7721 HCC xenografts. Collectively, these results suggested that NKG2D-BBz CAR-T cells could potently eliminate NKG2DL-high HCC cells both in vitro and in vivo, thereby providing a promising therapeutic intervention for patients with NKG2DL-positive HCC. |
| 收录类别 | sci
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13601
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| 专题 | 科研部门_肿瘤干细胞生物学（赵旭东）
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推荐引用方式
GB/T 7714 |
Sun, B,Yang, D,Dai, HJ,et al. Eradication of Hepatocellular Carcinoma by NKG2D-Based CAR-T Cells[J]. CANCER IMMUNOLOGY RESEARCH,2019,7(11):1813-1823.
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| APA |
Sun, B.,Yang, D.,Dai, HJ.,Liu, XY.,Jia, R.,...&Zhao, XD.(2019).Eradication of Hepatocellular Carcinoma by NKG2D-Based CAR-T Cells.CANCER IMMUNOLOGY RESEARCH,7(11),1813-1823.
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| MLA |
Sun, B,et al."Eradication of Hepatocellular Carcinoma by NKG2D-Based CAR-T Cells".CANCER IMMUNOLOGY RESEARCH 7.11(2019):1813-1823.
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