Induced CD20 Expression on B-Cell Malignant Cells Heightened the Cytotoxic Activity of Chimeric Antigen Receptor Engineered T Cells
Induced CD20 Expression on B-Cell Malignant Cells Heightened the Cytotoxic Activity of Chimeric Antigen Receptor Engineered T Cells
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B 细胞恶性肿瘤细胞上诱导的 CD20 表达增强了嵌合抗原受体工程化 T 细胞的细胞毒活性
DOI：
10.1089/hum.2018.119
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发表时间：
2019
影响因子：
4.2
通讯作者：
Wang Jianxiang
中科院分区：
文献类型：
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作者：
Xu Yingxi;Li Saisai;Wang Ying;Liu Jia;Mao Xinhe;Xing Haiyan;Tian Zheng;Tang Kejing;Liao Xiaolong;Rao Qing;Xiong Dongsheng;Wang Min;Wang Jianxiang
CD 20是CD 20 + B细胞恶性细胞的有效免疫治疗靶点。单克隆抗体，特别是利妥昔单抗，已成为治疗B细胞恶性肿瘤如非霍奇金淋巴瘤的常规策略。然而，用单克隆抗体治疗不足以克服难治性/复发问题。嵌合抗原受体工程化T细胞（CAR-T）近年来对淋巴细胞白血病表现出良好的治疗效果。在这项研究中，构建了CD 20特异性CAR，并通过CD 107 a脱粒，促炎细胞因子产生和体外和体内真实溶解能力评估了CD 20 CAR-T细胞对B细胞恶性细胞的细胞毒性功效。发现CD 20 CAR-T细胞对CD 20高表达细胞具有更强的细胞毒能力。此外，当使用组蛋白去乙酰化酶抑制剂通过诱导CD 20启动子位点上H3 K9的乙酰化来增强B细胞恶性细胞表面CD 20抗原的表达时，显示CD 20 CAR-T细胞对组蛋白去乙酰化酶抑制剂处理的B细胞恶性细胞的细胞毒性显著增强。
CD20 is an effective immunotherapy target for CD20+B-cell malignant cells. Monoclonal antibody, especially rituximab, has been a conventional strategy in the treatment of B-cell malignancies such as non-Hodgkin's lymphoma. However, treatment with monoclonal antibodies has not been enough to overcome the refractory/relapse problems. Chimeric antigen receptor engineered T (CAR-T) cells have exhibited excellent therapeutic effect on lymphocytic leukemia in recent years. In this study, a CD20-specific CAR was constructed and the cytotoxic efficacy of CD20 CAR-T cells on B-cell malignant cells was evaluated by CD107a degranulation, pro-inflammation cytokine production, and true lytic abilityin vitroandin vivo. It was found that CD20 CAR-T cells possessed stronger cytotoxic ability against CD20 highly expressed cells. Furthermore, when histone deacetylase inhibitor was used to enhance the expression of CD20 antigen on the surface of B-cell malignant cells via inducing acetylation of H3K9 on CD20 promoter site, it revealed that the cytotoxicity of CD20 CAR-T cells against histone deacetylase inhibitor–treated B-cell malignant cells was significantly enhanced.