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

Autor: Bing Liu, Zhen‑Dong Yu, Zheng‑Zhi Liu, Mei‑Ling Zhou, Wen‑Bin Gao, Xue‑Mei Chen, Zhu Li, Tao Liu, Jian‑Wei Lin
Rok vydání: 2019
Předmět:
Cytotoxicity
Immunologic
0301 basic medicine
Cancer Research
medicine.medical_treatment
Apoptosis
NK cells
Immunotherapy
Adoptive
Biochemistry
Mice
chemistry.chemical_compound
0302 clinical medicine
Cytotoxic T cell
Receptors
Chimeric Antigen
chimeric antigen receptor
Liver Neoplasms
Articles
Hep G2 Cells
Proto-Oncogene Proteins c-met
Molecular Imaging
Killer Cells
Natural
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Cytokines
Molecular Medicine
immunotherapy
Liver cancer
C-Met
T cell
Receptors
Antigen
T-Cell
liver cancer
03 medical and health sciences
Antigen
Cell Line
Tumor
Genetics
medicine
Animals
Humans
Molecular Biology
c-MET
business.industry
Cancer
Immunotherapy
medicine.disease
Xenograft Model Antitumor Assays
Chimeric antigen receptor
Disease Models
Animal
030104 developmental biology
chemistry
Cancer research
business
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
DOI: 10.3892/mmr.2019.10529
Popis: 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.
Databáze: OpenAIRE
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