NKG2D公司
嵌合抗原受体
细胞毒性
免疫系统
抗体
癌症研究
抗原
癌细胞
免疫疗法
生物
免疫学
化学
癌症
体外
生物化学
遗传学
作者
Changjiang Guo,Dong Meng,Xiang Wang,Yu J,Xin Jin,Siyuan Cheng,Feiyan Cui,Yifan Qian,Qiyu Bao,Lin Zhi,Zhiyuan Niu,Mingfeng Li,Wuling Zhu
标识
DOI:10.1016/j.bbrc.2024.149918
摘要
Chimeric antigen receptor (CAR)-modified immune cells have emerged as a promising approach for cancer treatment, but single-target CAR therapy in solid tumors is limited by immune escape caused by tumor antigen heterogeneity and shedding. Natural killer group 2D (NKG2D) is an activating receptor expressed in human NK cells, and its ligands, such as MICA and MICB (MICA/B), are widely expressed in malignant cells and typically absent from healthy tissue. NKG2D plays an important role in anti-tumor immunity, recognizing tumor cells and initiating an anti-tumor response. Therefore, NKG2D-based CAR is a promising CAR candidate. Nevertheless, the shedding of MICA/B hinders the therapeutic efficacy of NKG2D-CARs. Here, we designed a novel CAR by engineering an anti-MICA/B shedding antibody 1D5 into the CAR construct. The engineered NK cells exhibited significantly enhanced cytotoxicity against various MICA/B-expressing tumor cells and were not inhibited by NKG2D antibody or NKG2D-Fc fusion protein, indicating no interference with NKG2D-MICA/B binding. Therefore, the developed 1D5-CAR could be combined with NKG2D-CAR to further improve the obstacles caused by MICA/B shedding.
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