CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo
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Updated: Oct 5, 2025
Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
Manting Liu1, Wensou Huang1, Yongjian Guo1
1Department of Minimally Invasive Interventional Radiology and Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
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.
Insights
Chimeric antigen receptor (CAR) NK-92 cells targeting Delta-like ligand 3 (DLL3) show promise for treating small cell lung cancer (SCLC). These DLL3-CAR NK-92 cells effectively reduced tumors in preclinical models with good safety, offering a potential new SCLC therapy.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Small cell lung cancer (SCLC) presents significant challenges due to high relapse rates, drug resistance, and limited therapeutic options.
- Chimeric antigen receptor (CAR)-modified natural killer (NK) cells are an emerging immunotherapy with potential against various cancers.
- The specific application of CAR NK cells in SCLC treatment remains largely unexplored.
Purpose of the Study:
- To develop and evaluate Delta-like ligand 3 (DLL3)-specific CAR NK-92 cells for their efficacy in treating SCLC.
- To investigate DLL3 as a viable target for CAR NK cell-based immunotherapy in SCLC.
Main Methods:
- Development of DLL3-specific CAR NK-92 cells.
- In vitro assessment of cytotoxicity and cytokine production against DLL3-positive SCLC cell lines.
- In vivo evaluation of DLL3-CAR NK-92 cell efficacy and safety in pulmonary metastasis and subcutaneous SCLC xenograft models.
Main Results:
- DLL3-CAR NK-92 cells demonstrated significant in vitro cytotoxicity and cytokine release against DLL3+ SCLC cells.
- In vivo studies showed tumor regression in pulmonary metastasis and subcutaneous models with a favorable safety profile.
- Detection of substantial tumor infiltration by DLL3-CAR NK-92 cells in SCLC xenografts.
Conclusions:
- DLL3-CAR NK-92 cells exhibit potent antitumor activity against SCLC in preclinical models.
- DLL3-targeted CAR NK-92 cell therapy represents a promising and potentially safe strategy for SCLC treatment.
- Further investigation into DLL3-CAR NK-92 cells is warranted for clinical development in SCLC.
