CELL INTELLIGENCE · 肿瘤细胞治疗研究

Constantly stimulated by the tumor microenvironment (TME), programmed death 1 (PD 1) is elevated, and it interacts with PD ligand 1 (PD L1), rendering chimeric antigen receptor (CAR) T cells dysfunctional. Hence, CAR T cells immune to PD 1 induced immunosuppression were constructed to improve the function of CAR T cells in hepatocellular carcinoma (HCC). Double target CAR T cells, targeting glypican 3 (GPC3) [a tumour-associated antigen (TAA)] and hindering PD 1 PD L1 binding, were established. The expression of GPC3, PD L1, and inhibitory receptors was measured using flow cytometry. The cytotoxicity, cytokine release, and differentiation level of CAR T cells were determined using lactate dehydrogenase release assay, enzyme linked immunosorbent assay, and flow cytometry, respectively. HCC cells were targeted and eliminated by double target CAR T cells. These double target CAR T cells limit PD 1 PD L1 binding and sustain cytotoxicity to PD L1 + HCC cells. The relatively low IR expression and differentiation level in double target CAR T cells in tumour tissues induced tumour suppression and extended survival in PD L1 + HCC TX models, as opposed to their single target counterparts. The results of the present study suggested that the newly constructed double target CAR T cells exhibit stronger tumour suppressing effects in HCC than their single target counterparts, which are common, suggesting the potential of strengthening CAR T cell activity in HCC treatment.