Journal
CELL PROLIFERATION
Volume 53, Issue 8, Pages -Publisher
WILEY
DOI: 10.1111/cpr.12858
Keywords
chimeric antigen receptor-engineered natural killer cells; human epidermal growth factor receptor; triple-negative breast cancer; xenograft mouse models
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Funding
- China Postdoctoral Science Foundation [2019M661940]
- Foundation for Young Scholars of Jiangsu Province, China [BK20190194]
- Jiangsu Province Postdoctoral Science Foundation [1188004004]
- National Natural Science Foundation of China [81701332]
- Independent program of Chinese Academy of Sciences [Y852126105]
- Key Research and Development Program of Jiangsu Province,China [BE2017669, BE2018668]
- Major Innovative Research Team of Suzhou,China [ZXT2019007]
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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.
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