Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells
Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells
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DOI：
10.21873/anticanres.12824
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发表时间：
2018-09-01
影响因子：
2
通讯作者：
Nakase, Hiroyuki
中科院分区：
文献类型：
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作者：
Murakami, Toshiharu;Nakazawa, Tsutomu;Nakase, Hiroyuki
背景/目的：自然杀伤（NK）细胞被认为是潜在的抗肿瘤效应细胞。本研究的目的是建立一种新型的针对表达表皮生长因子受体变异体 III (EGFRvIII) 的肿瘤的新型嵌合抗原受体 (CAR) NK 细胞系 (CAR-KHYG-1)，并研究 EGFRvIII 特异性 CAR-KHYG-1 (EvCAR-KHYG-1) 的抗肿瘤活性。材料和方法：EvCAR-KHYG-1 通过 EvCAR 基因的自失活慢病毒转导和基于磁珠的表达 EvCAR 的 NK 细胞纯化而建立。使用胶质母细胞瘤 (GBM) 细胞系（表达 EGFRvIII 和不表达 U87MG）中的生长抑制和凋亡检测分析来评估 EvCAR-KHYG-1 的抗肿瘤作用。结果：研究结果表明，EvCAR-KHYG-1 以表达 EGFRvIII 的特定方式通过细胞凋亡抑制 GBM 细胞生长。结论：这是第一个基于人NK细胞系KHYG-1建立CAR NK细胞系的研究。 EvCAR-KHYG-1 治疗可能是 GBM 患者的有效治疗选择。
Background/Aim: Natural killer (NK) cells are considered potential antitumor effector cells. The aim of this study was to establish a novel type of a chimeric antigen receptor (CAR) NK cell line (CAR-KHYG-1) specific for epidermal growth factor receptor variant III (EGFRvIII)-expressing tumors and investigate the anti-tumor activity of EGFRvIII-specific-CAR-KHYG-1 (EvCAR-KHYG-1). Materials and Methods: EvCAR-KHYG-1 was established by self-inactivated lentiviral-based transduction of the EvCAR gene and magnetic bead-based purification of EvCAR-expressing NK cells. The anti-tumor effects of EvCAR-KHYG-1 were evaluated using growth inhibition and apoptosis detection assays in glioblastoma (GBM) cell lines (EGFRvIII-expressing and non-expressing U87MG). Results: The findings demonstrated that EvCAR-KHYG-1 inhibited GBM cell-growth via apoptosis in an EGFRvIII-expressing specific manner. Conclusion: This is the first study to establish a CAR NK cell line based on the human NK cell line KHYG-1. Therapy with EvCAR-KHYG-1 may be an effective treatment option for GBM patients.