CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CSF1-CAR Specifically Targets CSF1R + Pancreatic Cancer Cells and Tumor-Associated Macrophages.
CSF1-CAR Specifically Targets CSF1R + Pancreatic Cancer Cells and Tumor-Associated Macrophages.
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强免疫抑制性肿瘤微环境和非特异性靶点是恶性肿瘤CAR-T 细胞治疗面临的问题。GEPIA数据库显示,CSF1R在胰腺癌组织中的表达高于正常组织;M2巨噬细胞是造成免疫抑制性肿瘤微环境(TME)的主要因素,这提示CSF1R是合适抗原。CSF1是CSF1R的天然配体,因此我们构建了CSF1-CAR,并在体外检测其对肿瘤细胞和巨噬细胞的细胞毒效应。结果显示,CSF1-CAR-T 细胞可依赖CSF1R表达裂解肿瘤细胞。同时,CSF1-CAR-T 也可裂解CSF1R阳性M2巨噬细胞,提示CSF1-CAR-T 细胞既能清除肿瘤细胞,也能重塑TME。
A highly suppressive tumor immune microenvironment and nonspecific target endow malignant tumors with CAR-T cells. CSF1R is highly expressed on pancreatic cancer tissues compares with normal tissues in GEPIA database and M2 macrophages mainly contributing to the suppressive tumor microenvironment (TME), suggesting that CSF1R is a suitable antigen. CSF1 is the natural ligand of CSF1R, so we constructed a CSF1-CAR and tested its cytotoxic effect on tumor cells and macrophages in vitro.
Our results demonstrated that CSF1-CAR-T cells can lyse tumor cells dependent on CSF1R expression. Meanwhile, CSF1-CAR-T also lyse CSF1R + M2 macrophages, suggesting that CSF1-CAR-T cells play a role in eliminating tumor cells and remodeling the TME.
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