| T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells |
| Yang, D; Su, B ; Dai, HJ; Li, WX; Shi, L; Zhang, PX; Li, SR; Zhao, XD
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| 2019
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| 发表期刊 | JOURNAL FOR IMMUNOTHERAPY OF CANCER
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| ISSN | 2051-1426
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| 卷号 | 7 |
| 摘要 | Background: Traditional therapies fail to cure most glioblastoma patients and the 5-year survival rate is less than 10%, highlighting need for new therapeutic approaches. The natural killer group 2 member D ligands (NKG2DLs) are highly expressed in glioblastomas and are considered promising targets for chimeric antigen receptor (CAR) T-cell therapy. The aim of this study was to investigate the effect of NKG2D-expressing CAR-T cells on glioblastomas and glioblastoma stem cells. Methods: The expression of NKG2DLs was analyzed by flow cytometry and immunohistochemistry. NKG2D-BBz CAR, containing the extracellular domain of NKG2D, was constructed and delivered into T cells by lentiviral particles. In vitro cytotoxicity of the CAR-T cells was assessed by flow cytometry. Release of cytokine, perforin and granzyme B was quantified using enzyme-linked immunosorbent assay kits. The therapeutic efficacy of NKG2D-BBz CAR-T cells in vivo was evaluated using subcutaneous tumor models. The safety of the CAR was analyzed by investigating the effects on proliferation, apoptosis, and karyotype. Results: Our data confirmed the high expression of NKG2DLs in human glioblastoma cells, cancer stem cells, and tumor samples. Further, the NKG2D-BBz CAR-T cells efficiently lysed glioblastoma cells and cancer stem cells in vitro and produced high levels of cytokines, perforin, and granzyme B. The CAR-T cells markedly eliminated xenograft tumors in vivo and did not exhibit significant treatment-related toxicity in the treated mice. The CAR expression also did not exert any obvious effects on cell proliferation, apoptosis, and genomic stability. Conclusion: Our findings demonstrated that NKG2D CAR-T cells targeted glioblastoma cells and cancer stem cells in an NKG2D-dependent manner, supporting the use of CAR-T therapy in glioblastoma therapeutic strategies. |
| 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/152453/13604
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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 |
Yang, D,Su, B,Dai, HJ,et al. T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells[J]. JOURNAL FOR IMMUNOTHERAPY OF CANCER,2019,7.
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| APA |
Yang, D.,Su, B.,Dai, HJ.,Li, WX.,Shi, L.,...&Zhao, XD.(2019).T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells.JOURNAL FOR IMMUNOTHERAPY OF CANCER,7.
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| MLA |
Yang, D,et al."T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells".JOURNAL FOR IMMUNOTHERAPY OF CANCER 7(2019).
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