Development of c‑MET‑specific chimeric antigen receptor‑engineered natural killer cells with cytotoxic effects on human liver cancer HepG2 cells

Liu,Bing; Liu,Zheng‑Zhi; Zhou,Mei‑Ling; Lin,Jian‑Wei; Chen,Xue‑Mei; Li,Zhu; Gao,Wen‑Bin; Yu,Zhen‑Dong; Liu,Tao

doi:10.3892/mmr.2019.10529

Development of c‑MET‑specific chimeric antigen receptor‑engineered natural killer cells with cytotoxic effects on human liver cancer HepG2 cells

Authors:
- Bing Liu
- Zheng‑Zhi Liu
- Mei‑Ling Zhou
- Jian‑Wei Lin
- Xue‑Mei Chen
- Zhu Li
- Wen‑Bin Gao
- Zhen‑Dong Yu
- Tao Liu
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Affiliations: Department of Biotherapy and Oncology, Shenzhen Luohu People's Hospital, Shenzhen, Guangdong 518001, P.R. China, Department of Laboratory, Women and Children Health Institute of Futian, Shenzhen, Guangdong 518045, P.R. China, Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
Published online on: July 25, 2019 https://doi.org/10.3892/mmr.2019.10529
Pages: 2823-2831
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In recent years, cellular immunotherapy has served an important role in the combined treatment of hepatocellular carcinoma. The possibility of specific cell therapies for the treatment of solid tumours has been further explored following the success of chimeric antigen receptor (CAR)‑T cell therapy in the treatment of haematological tumours. The present study aimed to evaluate the specificity and efficiency of c‑MET‑targeted CAR‑NK cell immunotherapy on human liver cancer in vitro. A CAR structure that targeted and recognised a c‑MET antigen was constructed. c‑MET‑CAR was transferred into primary NK cells using lentiviral infection. c‑MET‑positive HepG2 cells were used as an in vitro study model. The cytotoxicity assay results revealed that c‑MET‑CAR‑NK cells exhibited more specific cytotoxicity for HepG2 cells with high c‑MET expression compared with the lung cancer cell line H1299, which has low levels of c‑MET expression. The results of the present study demonstrated that c‑MET may be a specific and effective target for human liver cancer cell CAR‑NK immunotherapy. Based on these results, CAR‑NK cell‑based immunotherapy may provide a potential biotherapeutic approach for liver cancer treatment in the future.

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