期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 112, 期 4, 页码 901-911出版社
OXFORD UNIV PRESS
DOI: 10.1002/JLB.5MA0122-467R
关键词
chimeric antigen receptor; delta-like ligand 3; NK-92 cells; SCLC
资金
- National Natural Science Foundation of China [81873920, 82001930]
- Science and Technology Program of Guangzhou [202002030135, 202102010082]
- PhD Start-up Fund of the Second Affiliated Hospital of Guangzhou Medical University
- National Key R&D Program of China [2019YFA0904400]
- Shenzhen Science and Technology Project [SGDX2020110309280301]
- Science and Technology Development Fund, Macau SAR [FDCT/0043/2021/A1]
- University of Macau [MYRG2019-00069-FHS]
- Basic and Applied Basic Research Foundation of Guangdong Province [2020A1515110654]
In this study, DLL3-specific NK-92 cells were developed and it was found that they have potential therapeutic effects on SCLC.
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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