GPC3-CAR-T疗法干预甲胎蛋白阳性胃癌的体外研究

In vitro study on the intervention of alpha-fetoprotein producing gastric carcinoma with GPC3-CAR-T therapy

为了探究治疗甲胎蛋白阳性胃癌(alpha-fetoprotein producing gastric carcinoma,AFPGC)的新方法,以临床病理筛选的AFPGC患者为研究对象,选取AFP、磷脂酰肌醇聚糖3(glypican 3,GPC3)高表达胃癌细胞FU97为阳性对照,AFP、GPC3不表达胃癌细胞MGC-803为阴性对照,构建靶向GPC3嵌合抗原受体修饰的T细胞(chimeric antigen receptor-modified T cell,CAR-T)对上述肿瘤细胞进行体外杀伤试验并检测CAR-T分泌细胞因子的能力。结果显示,在10∶1效靶比状态下,GPC3-CAR-T对GPC3阳性的AFPGC和FU97细胞具有显著的杀伤效应,而对GPC3阴性的MGC-803细胞无显著杀伤效应。同时,在靶细胞为AFPGC或FU97时,GPC3-CAR-T分泌IL-2和IFN-γ水平较靶细胞为MGC-803时显著升高(P<0.05)。该研究提示,AFPGC对GPC3-CAR-T体外干预治疗敏感,GPC3-CAR-T疗法具有进一步深入研究的价值。

To explore a new approach to treat alpha-fetoprotein producing gastric carcinoma(AFPGC),selected clinicopathologically identified AFPGC as the research object,and selected FU97 gastric carcinoma cells with positive expression of AFP and glypican 3(GPC3)as the positive control group while MGC-803 gastric carcinoma cells with negative expression of AFP and GPC3 as the negative control.GPC3 chimeric antigen receptor-modified T cells(CAR-T)were constructed to carry out in vitro killing experiment of tumor cells.And cytokine released by CAR-T cells was also evaluated.The results showed that at 10∶1 effect target ratio,GPC3-CAR-T cells had a significant killing effect on GPC3-positive AFPGC and FU97 cells,but not on GPC3-negative MGC-803 cells.When the target cell was AFPGC or FU97,the secretion of IL-2 and IFN-γby GPC3-CAR-T cells was significantly increased than MGC-803 T cell(P<0.05).All results in our study indicate that AFPGC is sensitive to GPC3-CAR-T intervention and GPC3-CAR-T therapy is worth of further study.