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

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-N K 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-N K immunotherapy. Based on these results, CAR-N K cell-based immunotherapy may provide a potential biotherapeutic approach for liver cancer treatment in the future.