免疫疗法
体内
生物
转移
细胞
细胞培养
癌症研究
体外
细胞生物学
细胞毒性T细胞
细胞凋亡
嵌合抗原受体
细胞生长
肺癌
免疫学
作者
Manting Liu,Wensou Huang,Yongjian Guo,Yubo Zhou,Cheng Zhi,Jingwu Chen,Junping Li,Jinping He,Hui Lian,Jingwen Zhou,Xiaodie Ye,Yuling Hu,Hong Hu,Zhaoyuan Liu,Jingjun Huang,Liteng Lin,Mingyue Cai,Xiaobin Wang,Jingzhen Huang,Zhenfeng Zhang,Kangshun Zhu,Qi Zhao,Bihui Cao
标识
DOI:10.1002/jlb.5ma0122-467r
摘要
Small cell lung cancer (SCLC) is characterized by a high relapse rate, drug tolerance, and limited treatment choices. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential applications have not been explored in SCLC. Delta-like ligand 3 (DLL3) has been reported to be overexpressed in SCLC and may be a rational target for CAR NK immunotherapy. In this study, we developed DLL3-specific NK-92 cells and explored their potential in the treatment of SCLC. A coculture of DLL3+ SCLC cell lines with DLL3-CAR NK-92 cells exhibited significant in vitro cytotoxicity and cytokine production. DLL3-CAR NK-92 cells induced tumor regression in an H446-derived pulmonary metastasis tumor model under a good safety threshold. The potent antitumor activities of DLL3-CAR NK-92 cells were observed in subcutaneous tumor models of SCLC. Moreover, obvious tumor-infiltrated DLL3-CAR NK-92 cells were detected in DLL3+ SCLC xenografts. These findings indicate that DLL3-CAR NK-92 cells might be a potential strategy for the treatment of SCLC.
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