HGF-Based CAR-T Cells Target Hepatocellular Carcinoma Cells That Express High Levels of c-Met

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	HGF-Based CAR-T Cells Target Hepatocellular Carcinoma Cells That Express High Levels of c-Met
	Ma, HY; Wei, WW; Liang, DD; Xu, X; Yang, D; Wang, Q; Wang, Y; Wei, Q; Sun, B; Zhao, XD
	2023
发表期刊	IMMUNOLOGICAL INVESTIGATIONS
ISSN	0882-0139
卷号	52 期号:6 页码:735-748
摘要	Background: CAR-T is emerging as an effective treatment strategy for hematologic malignancies, however its effectiveness for treating solid tumors, such as Hepatocellular Carcinoma (HCC) is limited. Here, we screened a variety of CAR-T cells that target c-Met to investigate their potential to induce HCC cell death in vitro. Methods: Human T cells were transduced to express CARs by lentiviral vector transfection. c-Met expression in human HCC cell lines and CARs expression were monitored by flow cytometry. Tumor cell killing was evaluated by Luciferase Assay System Kit. The concentrations of cytokine were tested by Enzyme-linked immunosorbent assays. Knock down and overexpression studies targeting c-Met were conducted to assess the targeting specificity of CARs. Results: We found that CAR T cells expressing a minimal amino-terminal polypeptide sequence comprising the first kringle (kringle 1) domain (denoted as NK1 CAR-T cells), efficiently killed HCC cell lines that expressed high levels of the HGF receptor c-Met. Furthermore, we report that while NK1 CAR-T cells were efficient at targeting SMMC7221 cells for destruction, and its potency was significantly attenuated in parallel experiments with cells stably expressing short hairpin RNAs (shRNAs) that suppressed c-Met expression. Correspondingly, overexpression of c-Met in the embryonic kidney cell line HEK293T led to their enhanced killing by NK1 CAR-T cells. Conclusion: Our studies demonstrate that a minimal amino-terminal polypeptide sequence comprising the kirngle1 domain of HGF is highly relevant to the design of effective CAR-T cell therapies that kill HCC cells expressing high levels of c-Met.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14395
专题	管理、支撑部门_实验动物中心
推荐引用方式 GB/T 7714	Ma, HY,Wei, WW,Liang, DD,et al. HGF-Based CAR-T Cells Target Hepatocellular Carcinoma Cells That Express High Levels of c-Met[J]. IMMUNOLOGICAL INVESTIGATIONS,2023,52(6):735-748.
APA	Ma, HY.,Wei, WW.,Liang, DD.,Xu, X.,Yang, D.,...&Zhao, XD.(2023).HGF-Based CAR-T Cells Target Hepatocellular Carcinoma Cells That Express High Levels of c-Met.IMMUNOLOGICAL INVESTIGATIONS,52(6),735-748.
MLA	Ma, HY,et al."HGF-Based CAR-T Cells Target Hepatocellular Carcinoma Cells That Express High Levels of c-Met".IMMUNOLOGICAL INVESTIGATIONS 52.6(2023):735-748.

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2024061703.pdf（3083KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文