Chimeric antigen receptor T cells targeting CD147 for non-small cell lung cancer therapy.
Chimeric antigen receptor T cells targeting CD147 for non-small cell lung cancer therapy.
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DOI：
10.1016/j.tranon.2021.101309
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发表时间：
2022-03
影响因子：
5
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Chen XH;Chen R;Shi MY;Tian RF;Zhang H;Xin ZQ;Chen ZN;Wang K
肿瘤特异性抗原CD147在非小细胞肺癌的进展中起关键作用。慢病毒转染法成功构建CD147-CART细胞。CD147-CART细胞在体外表现出强大的细胞毒性和细胞因子的产生。CD147-CART细胞在CDX和PDX模型中对非小细胞肺癌细胞均具有较强的体内抗肿瘤活性，且无毒副作用。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，嵌合抗原受体T细胞(CART)越来越受到重视，并在血液系统恶性肿瘤的治疗中取得了突出的贡献。然而，CART治疗非小细胞肺癌进展缓慢，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在非小细胞肺癌中的重要作用。检测CD147在人NSCLC细胞系和NSCLC组织中的表达水平。同时，构建并鉴定了CD147-Cart。用细胞毒试验和细胞因子分泌试验评价CD147-CART的疗效。我们还构建了细胞来源的异种移植(CDX)模型和患者来源的异种移植(PDX)模型，以进一步研究CD147-CART在体内的安全性和有效性。我们的观察表明，CD147是NSCLC的一种特异性肿瘤抗原，在NSCLC的进展中起着重要作用，可以作为CART治疗NSCLC的靶点。CD147-CART细胞在体外表现出较强的细胞毒作用和细胞因子的产生，提示CD147-CART细胞对NSCLC肿瘤细胞具有较强的抗肿瘤活性。重要的是，CD147-CART细胞在体内对非小细胞肺癌细胞具有很强的抗肿瘤活性，在CDX和PDX模型中都是如此，并且没有不良反应。结果表明，CD147-CART免疫疗法治疗非小细胞肺癌安全有效，是治疗非小细胞肺癌的理想药物。
Tumor specific antigen CD147 plays a critical role in NSCLC progression. CD147-CART cells are successfully constructed through lentiviral transfection. CD147-CART cells exhibit robust cytotoxicity and cytokine production in vitro. CD147-CART cells have strong anti-tumor activity against NSCLC cells in vivo in both CDX and PDX models and no adverse side effects. 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.
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