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Updated: Dec 17, 2025
Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Targeting epidermal growth factor-overexpressing triple-negative breast cancer by natural killer cells expressing a
Yan Liu1,2,3, Yehui Zhou4, Kuo-Hsiang Huang1
1The Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology (SIBET), Chinese Academy of Sciences, Suzhou, China.
Objectives:
Traditional cancer therapy and regular immunotherapy are ineffective for treating triple-negative breast cancer (TNBC) patients. Recently, chimeric antigen receptor-engineered natural killer cells (CAR NK) have been applied to target several hormone receptors on different cancer cells to improve the efficacy of immunotherapy. Furthermore, epidermal growth factor receptor (EGFR) is a potential therapeutic target for TNBC. Here, we demonstrated that EGFR-specific CAR NK cells (EGFR-CAR NK cells) could be potentially used to treat patients with TNBC exhibiting enhanced EGFR expression.
Materials And Methods:
We investigated the cytotoxic effects of EGFR-CAR NK cells against TNBC cells in vitro and in vivo. The two types of EGFR-CAR NK cells were generated by transducing lentiviral vectors containing DNA sequences encoding the single-chain variable fragment (scFv) regions of the two anti-EGFR antibodies. The cytotoxic and anti-tumor effects of the two cell types were examined by performing cytokine release and cytotoxicity assays in vitro, and tumor growth assays in breast cancer cell line-derived xenograft (CLDX) and patient-derived xenograft (PDX) mouse models.
Results:
Both EGFR-CAR NK cell types were activated by TNBC cells exhibiting upregulated EGFR expression and specifically triggered the lysis of the TNBC cells in vitro. Furthermore, the two EGFR-CAR NK cell types inhibited CLDX and PDX tumors in mice.
Conclusions:
This study suggested that treatment with EGFR-CAR NK cells could be a promising strategy for TNBC patients.
Insights
Chimeric antigen receptor-engineered natural killer (CAR NK) cells targeting epidermal growth factor receptor (EGFR) show promise for treating triple-negative breast cancer (TNBC). EGFR-CAR NK cells effectively reduced TNBC tumors in preclinical models.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Triple-negative breast cancer (TNBC) remains challenging due to the ineffectiveness of traditional therapies and standard immunotherapies.
- Chimeric antigen receptor-engineered natural killer (CAR NK) cells offer a novel approach to cancer treatment by targeting specific cell receptors.
- Epidermal growth factor receptor (EGFR) is identified as a potential therapeutic target for TNBC.
Purpose of the Study:
- To evaluate the potential of epidermal growth factor receptor-specific CAR NK cells (EGFR-CAR NK cells) for treating TNBC.
- To investigate the efficacy of EGFR-CAR NK cells against TNBC models with high EGFR expression.
Main Methods:
- Two types of EGFR-CAR NK cells were generated using lentiviral vectors encoding anti-EGFR antibody fragments.
- In vitro studies assessed cytotoxic effects and cytokine release upon activation by TNBC cells.
- In vivo efficacy was evaluated using breast cancer cell line-derived xenograft (CLDX) and patient-derived xenograft (PDX) mouse models.
Main Results:
- EGFR-CAR NK cells were activated by TNBC cells expressing elevated EGFR.
- These cells demonstrated specific lysis of TNBC cells in vitro.
- EGFR-CAR NK cells significantly inhibited tumor growth in both CLDX and PDX mouse models.
Conclusions:
- EGFR-CAR NK cell therapy presents a promising new strategy for managing triple-negative breast cancer.
- This approach warrants further investigation for clinical application in TNBC patients.
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