来那度胺
嵌合抗原受体
细胞因子
细胞毒性
癌症研究
细胞培养
细胞生长
癌症免疫疗法
免疫疗法
化学
T细胞
生物
多发性骨髓瘤
免疫学
免疫系统
体外
生物化学
遗传学
作者
Zhixiong Wang,Guomin Zhou,Risu Na,Jiayu Fu,Yan Zou,Jiaxing Tang,Li Long,Hui Liu,Qian Liu,Xuekai Zhu
标识
DOI:10.1177/0963689720920825
摘要
Chimeric antigen receptor (CAR) T-cell immunotherapy still faces many challenges in the treatment of solid tumors, one of which is T-cell dysfunction or exhaustion. Immunomodulator lenalidomide may improve CAR T-cell function. In this study, the effects of lenalidomide on CAR T-cell functions (cytotoxicity, cytokine secretion, and cell proliferation) were investigated. Two different CAR T cells (CD133-specific CAR and HER2-specific CAR) were prepared, and the corresponding target cells including human glioma cell line U251 CD133-OE that overexpress CD133 and human breast cancer cell line MDA-MB-453 were used for functional assay. We found that lenalidomide promoted the killing of U251 CD133-OE by CD133-CAR T cells, the cytokine secretion, and the proliferation of CD133-CAR T cells. Lenalidomide also enhanced the cytotoxicity against MDA-MB-453 and the cytokine secretion of HER2-CAR T cells but did not affect their proliferation significantly. Furthermore, lenalidomide may regulate the function of CAR T cells by inducing the degradation of transcription factors Ikaros and Aiolos.
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