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J Leukoc Biol ; 112(4): 901-911, 2022 10.
Article in English | MEDLINE | ID: mdl-35088475

ABSTRACT

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.


Subject(s)
Lung Neoplasms , Receptors, Chimeric Antigen , Small Cell Lung Carcinoma , Cell Line, Tumor , Cytokines/metabolism , Humans , Intracellular Signaling Peptides and Proteins , Ligands , Lung Neoplasms/drug therapy , Membrane Proteins/metabolism , Neoplasm Recurrence, Local , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/metabolism
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