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体外评估基因未修饰的配体武装异体 NK 细胞治疗 EGFR 阳性胶质母细胞瘤

英文原题:In Vitro Evaluation of Genetically Unmodified Ligand-Armed Allogeneic Natural Killer Cells to Treat EGFR-Positive Glioblastoma.

PubMed 2025/02/11(内容时间) Cells Q2 · IF 6(JCR 2025)

研究概要

这些结果表明,携带Pin-EGFR的eNK细胞在体外对GBM细胞系具有潜在的有效治疗作用。

中文摘要

胶质母细胞瘤(GBMs)是致命的脑肿瘤,其中EGFR基因扩增或突变频繁检测到,并与不良预后相关。标准治疗为最大程度切除肿瘤,随后进行化疗和放疗。过去二十年间,患者生存率的微小改善主要归功于手术技术和放疗的更精确应用。在本研究中,脐带血来源并扩增的人同种异体自然杀伤(eNK)细胞与Fc工程化抗EGFR单克隆抗体(Pin-EGFR)预复合,形成Pin-EGFR武装的eNK细胞。Pin-EGFR武装的eNK细胞在体外显示出mAb锚定的持久性。此武装过程介导了针对GBM细胞系及患者来源细胞的特异性、快速且强效的NK细胞重定向细胞毒性,在符合GBM病理生理条件的模型中得以验证。这些结果证明了Pin-EGFR武装的eNK细胞在体外对GBM细胞系具有有效治疗的潜力。该产品代表了一种有前景的策略,旨在直接靶向GBM手术后切除边缘及边缘外残留的肿瘤组织,以改善患者护理。

展开英文摘要原文

Glioblastomas (GBMs) are lethal brain tumors in which EGFR gene amplification or mutation is frequently detected and is associated with poor prognosis. The standard of care is maximal resection followed by chemotherapy and radiation. Over the last twenty years, marginal improvements in patient survival have been achieved mainly through surgical techniques and the more accurate use of radiation. In this study, umbilical cord blood-derived and expanded human allogeneic natural killer (eNK) cells were pre-complexed to an Fc-engineered anti-EGFR monoclonal antibody (Pin-EGFR) to create Pin-EGFR-armed eNK cells. Pin-EGFR-armed eNK cells showed in vitro persistence of mAb anchoring. This arming process mediated specific, rapid and potent NK cell-redirected cytotoxicity against GBM cell lines and patient-derived cells in models consistent with the pathophysiological conditions of GBM. These results demonstrate the potential of Pin-EGFR-armed eNK cells to be an effective therapy against GBM cell lines in vitro. This product represents a promising strategy to directly target residual tumor tissue remaining at and beyond the resection margins immediately following GBM surgery to improve patient care.

论文信息

作者
Courot H、Rigal E、Adib N、Criton M、Cookson A、Fauvel B、Presumey J
单位
CYTEA BIO, 34790 Montpellier, France.France
文献类型
非美国政府资助研究
期刊
Cells2025 Feb 11
原文标识
PubMed 39996727 · DOI 10.3390/cells14040254