[Bioinformatic prediction and validation of cellular-mesenchymal epithelial transition(c-Met) as a target for chimeric antigen receptor T (CAR-T) cell therapy in the treatment of colorectal cancer].

Objective To explore the potential of the cell surface receptor c-Met as an effective target for chimeric antigen receptor T-cell (CAR-T) therapy in colorectal cancer. Methods The bioinformatics was used to analyze the specific expression of c-Met in colorectal adenocarcinoma (COAD) and its clinical significance. c-Met protein expression was detected by immunohistochemistry in tumor tissues obtained from colorectal cancer patients. Flow cytometry was utilized to assess the expression of c-Met in the HCT116 human colorectal cancer cell line. Additionally, primary T cells isolated from human peripheral blood mononuclear cells (PBMCs) were transduced with a lentivirus to generate second-generation CAR-T cells targeting c-Met, followed by an observation of the inhibitory effects of these c-Met-targeted CAR-T cells on HCT116 cells. Results Immunohistochemistry and bioinformatics data both demonstrated that c-Met was over-expressed in COAD, with patients exhibiting relatively lower expression showing better prognosis. In normal colonic tissue, c-Met was either expressed at low levels or not expressed. Flow cytometry revealed high expression of c-Met in HCT116 cells as well. The c-Met-targeted CAR-T cells were capable of specifically recognizing and targeting antigen-expressing tumor cells. CAR-T cells proliferated specifically under antigenic stimulation, exerting cytotoxic effects on cancer cells and releasing cytokines interleukin 2 (IL-2) and interferon-gamma (IFN-γ), thereby demonstrating the biological functions. Conclusion c-Met may be a promising therapeutic target in COAD; c-Met-targeted CAR-T cells demonstrate inhibitory effects on colorectal cancer cells in vitro.