肿瘤细胞治疗研究
英文原题：Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells.
Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells.
嵌合抗原受体工程化 T 细胞（CAR-T）疗法对血液肿瘤具有高疗效，但在实体瘤中尚未显示出令人满意的结果。
嵌合抗原受体工程化T细胞（CAR-T）疗法治疗血液系统癌症疗效较高，但用于实体瘤尚未获得令人满意的结果。因此，我们研究靶向癌胚抗原（CEA）的CAR-T疗法治疗胰腺腺癌（PDAC）的治疗作用。采用流式细胞术评估多种PDAC细胞系细胞膜上的CEA表达水平，并将细胞分为高、中、低表达组。通过多种PDAC细胞系功能实验评估CEA表达水平与抗CEA-CAR-T抗肿瘤效果的关系，观察到二者显著相关。我们建立PDAC原位异种移植小鼠模型并注射抗CEA-CAR-T；只有CEA高表达细胞系显示显著治疗效果。因此，CAR-T疗效与靶抗原表达水平相关。进一步回顾性分析PDAC患者病理结果发现，CEA免疫组化染色强度与肿瘤异质性相关。因此，活检或手术标本中的CEA表达水平可作为临床生物标志物，用于筛选接受抗CEA CAR-T疗法的PDAC患者。
Chimeric antigen receptor engineered T cell (CAR-T) therapy has high therapeutic efficacy against blood cancers, but it has not shown satisfactory results in solid tumors. Therefore, we examined the therapeutic effect of CAR-T therapy targeting carcinoembryonic antigen (CEA) in pancreatic adenocarcinoma (PDAC). CEA expression levels on the cell membranes of various PDAC cell lines were evaluated using flow cytometry and the cells were divided into high, medium, and low expression groups. The relationship between CEA expression level and the antitumor effect of anti-CEA-CAR-T was evaluated using a functional assay for various PDAC cell lines; a significant correlation was observed between CEA expression level and the antitumor effect. We created orthotopic PDAC xenograft mouse models and injected with anti-CEA-CAR-T; only the cell line with high CEA expression exhibited a significant therapeutic effect. Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy.
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