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探索 CAR-PBMCs:一种针对 EGFR 阳性肿瘤细胞的新策略

英文原题:Exploring CAR-PBMCs: A Novel Strategy Against EGFR-Positive Tumor Cells.

查看英文原题

Exploring CAR-PBMCs: A Novel Strategy Against EGFR-Positive Tumor Cells.

PubMed 2025/01/22(内容时间) Biomedicines Q2 · IF 4.5(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法在治疗血液系统恶性肿瘤方面显示出显著前景,但其在实体瘤,尤其是表达表皮生长因子受体(EGFR)的实体瘤中的应用仍然有限。本研究探讨CAR工程化外周血单个核细胞(PBMCs)作为针对EGFR阳性癌症的新型过继细胞疗法的潜力。

以MOI为50进行慢病毒转导,以生成特异性抗EGFR第二代CAR效应细胞。转导后的PBMCs用细胞因子和CD3/CD28磁珠刺激,以增强其增殖和活化。在不同效靶比下进行流式细胞术和实时细胞分析,以探讨CAR-PBMCs的细胞毒性潜力。

与未转导对照相比,CAR-PBMCs对EGFR阳性癌细胞系MDA-MB-468和SK-BR-3表现出更好的靶向性和细胞毒性,对同种异体PBMCs的影响不显著。

CAR-PBMCs作为EGFR阳性实体瘤的治疗策略具有相当大的潜力,值得进一步开展临床研究。

展开英文摘要原文

Background: Chimeric antigen receptor (CAR) T cell therapy has shown significant promise in treating hematological malignancies, yet its application in solid tumors, particularly those expressing the epidermal growth factor receptor (EGFR), remains limited.

This study investigates the potential of CAR-engineered peripheral blood mononuclear cells (PBMCs) as a novel adoptive cell therapy against EGFR-positive cancers. Methods: Lentiviral transduction at an MOI of 50 was performed to generate specific anti-EGFR second generation CAR-effector cells. The transduced PBMCs were stimulated with cytokines and CD3/CD28 beads to enhance their proliferation and activation.

Flow cytometric and real-time cell analysis were performed at various effector-to-target ratios to explore the cytotoxic potential of CAR-PBMCs. Results: CAR-PBMCs exhibited improved targeting and cytotoxicity against EGFR-positive cancer cell lines MDA-MB-468 and SK-BR-3, compared to untransduced controls, with unsignificant effects on allogeneic PBMCs. Conclusion: CAR-PBMCs hold considerable potential as a therapeutic strategy for EGFR-positive solid tumors, warranting further clinical investigation.

论文信息

作者
Tîrziu A、Gavriliuc OI、Bojin MF、Păunescu V
单位
Department of Functional Sciences, Immuno-Physiology and Biotechnologies Center, "Victor Babes" University of Medicine and Pharmacy, No. 2 Eftimie Murgu Square, 300041 Timisoara, Romania.Italy
期刊
Biomedicines2025 Jan 22
原文标识
PubMed 40002679 · DOI 10.3390/biomedicines13020264