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靶向 CD147 的 CAR-T 细胞用于非小细胞肺癌治疗

英文原题:Chimeric antigen receptor T cells targeting CD147 for non-small cell lung cancer therapy.

查看英文原题

Chimeric antigen receptor T cells targeting CD147 for non-small cell lung cancer therapy.

PubMed 2021/12/09(内容时间) Transl Oncol Q2 · IF 4.9(JCR 2025)

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中文摘要

非小细胞肺癌(NSCLC)是一种高度恶性的肿瘤,具有显著的死亡率和发病率。随着肿瘤免疫治疗的发展,CAR-T 细胞越来越受到关注,并在血液系统恶性肿瘤的治疗中取得了突出贡献。

然而,CAR-T 治疗NSCLC进展缓慢,需要进一步研究。在我们的研究中,我们进行了生物信息学分析,以评估CD147在NSCLC中的重要作用。在人NSCLC细胞系和NSCLC组织中检测了CD147的表达水平。

同时,构建并鉴定了CD147-CART。通过细胞毒性和细胞因子分泌实验评估CD147-CART的疗效。我们还构建了细胞源性异种移植(CDX)模型和患者源性异种移植(PDX)模型,用于进一步研究CD147-CART在体内的安全性和有效性。

我们的观察结果表明,CD147是NSCLC的一种特异性肿瘤抗原,在NSCLC进展中发挥重要作用,可作为NSCLC中CAR-T 治疗的靶点。CD147-CART细胞在体外表现出强大的细胞毒性和细胞因子产生,表明对NSCLC肿瘤细胞具有强效抗肿瘤活性。

重要的是,CD147-CART细胞在CDX和PDX模型中均对NSCLC细胞表现出强大的体内抗肿瘤活性,且无不良副作用。我们的研究结果表明,CD147-CART免疫治疗NSCLC安全有效,是治疗NSCLC的理想且有前景的医学补丁。

展开英文摘要原文

Non-small cell lung cancer (NSCLC) is a highly malignant tumor, with a significant mortality and morbidity. With the development of tumor immunotherapy, chimeric antigen receptor T cells (CART) gets increasingly attention and achieves prominent contributions in the treatment of hematologic malignancies.

However, CART therapy for NSCLC proceeds slowly and further researches need to be investigated. In our study, we performed bioinformatics analysis to evaluate the significant role of CD147 in NSCLC. The expression level of CD147 was detected in human NSCLC cell lines and NSCLC tissues. Meanwhile, CD147-CART was constructed and identified. Cell cytotoxicity and cytokine secretion were performed to evaluate the efficacy of CD147-CART.

We also constructed cell-derived xenograft (CDX) model and patient-derived xenograft (PDX) model, which was used to further investigate the safety and efficacy of CD147-CART in vivo.

Our observations show that CD147 is a specific tumor antigen of NSCLC and plays an essential role in NSCLC progression, which can be used as a target for CART therapy in NSCLC. CD147-CART cells exhibit robust cytotoxicity and cytokine production in vitro, suggesting a strong anti-tumor activity against NSCLC tumor cells.

Importantly, CD147-CART cells have strong anti-tumor activity against NSCLC cells in vivo in both CDX and PDX models and no adverse side effects.

Our findings show that CD147-CART immunotherapy for NSCLC is safe and effective, which is an ideal and promising medical patch for treating NSCLC.

论文信息

作者
Chen XH、Chen R、Shi MY、Tian RF、Zhang H、Xin ZQ、Chen ZN、Wang K
第一作者单位
National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.China
通讯作者单位
National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China. Electronic address: wangke@fmmu.edu.cn.China
期刊
Translational oncology2022 Feb
原文标识
PubMed 34896852 · DOI 10.1016/j.tranon.2021.101309