c-Met 特异性 CAR-T 细胞作为非小细胞肺癌细胞 A549 的靶向治疗

Non-small cell lung cancer (NSCLC) is considered to be one of the most prevalent and fatal malignancies, with a poor survival rate. Chimeric antigen receptor T cell (CAR-T) cell therapy is one of the most exciting directions in the field of Cellular immunotherapy.

Therefore, CAR-T cells that target c-Met have been developed for use in NSCLC therapy and might be a potential therapeutic strategy. The anti c-Met scFv structure was fused with the transmembrane and intracellular domains. Using a lentiviral vector to load the c-Met CAR gene, then transfected the c-Met CAR lentiviral into human T cells to obtain the second generation c-Met CAR-T expressing CARs stably. In vitro co-culture, experiments revealed that CAR-T cells have high proliferative activity and the potential to secrete cytokines (IL-2, TNF- , and IFN- ). c-Met CAR-T cells showed special cellular cytotoxicity in LDH release assay.

A subcutaneous tumor model in nude mice was used to test the anticancer effectiveness of c-met CAR-T cells in vivo. For c-Met positive NSCLC tissue, according to tumor volume, weight, fluorescence intensity, and immunohistochemical detection, c-Met CAR-T cells had stronger tumor growth suppression compared to untransduced T cells.

HE staining revealed that c-Met CAR-T cells did not produced side effects in nude mice. Taken together, we provided useful method to generate c-Met CAR- T cells, which exhibit enhanced cytotoxicity against NSCLC cells in vitro and in vivo.

Thus, providing a new therapeutic avenue for treating NSCLC clinically. Highlights (1) c-Met CAR-T capable of stably expressing c-Met CARs were constructed. (2) c-Met CAR-T have strong anti-tumor ability and proliferation ability in vitro. (3) c-Met CAR-T can effectively inhibit the growth of A549 cells subcutaneous xenografts.