CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
具有内置 CD47 阻断剂的 CAR 巨噬细胞对抗肿瘤抗原异质性，并通过交叉呈递激活 T 细胞
英文原题：CAR macrophages with built-In CD47 blocker combat tumor antigen heterogeneity and activate T cells via cross-presentation.
查看英文原题
CAR macrophages with built-In CD47 blocker combat tumor antigen heterogeneity and activate T cells via cross-presentation.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
基于巨噬细胞的肿瘤细胞治疗已引起广泛关注。然而，工程化巨噬细胞靶向肿瘤异质性并调节适应性免疫的能力仍不明确。在此，利用髓系抗体依赖性细胞吞噬生物学和吞噬检查点阻断，我们报道了增强型合成吞噬受体（eSPR），其将FcRγ驱动的吞噬性嵌合抗原受体（CAR）与内置分泌型CD47阻断剂整合在一起。eSPR工程化使巨噬细胞能够对抗肿瘤抗原异质性。通过腺病毒载体转导，eSPR巨噬细胞内在性地被印迹为促炎表型并抵抗肿瘤性极化。在转录组和表型上，eSPR巨噬细胞引发更有利的肿瘤免疫景观。在机制上，eSPR巨噬细胞通过吞噬依赖性抗原交叉呈递在原位刺激CD8 T细胞。我们还在人原代巨噬细胞中验证了eSPR系统的功能。
展开英文摘要原文
Macrophage-based cancer cellular therapy has gained substantial interest.
However, the capability of engineered macrophages to target cancer heterogeneity and modulate adaptive immunity remains unclear.
Here, exploiting the myeloid antibody-dependent cellular phagocytosis biology and phagocytosis checkpoint blockade, we report the enhanced synthetic phagocytosis receptor (eSPR) that integrate FcRγ-driven phagocytic chimeric antigen receptors (CAR) with built-in secreted CD47 blockers.
The eSPR engineering empowers macrophages to combat tumor antigen heterogeneity. Transduced by adenoviral vectors, eSPR macrophages are intrinsically pro-inflammatory imprinted and resist tumoral polarization. Transcriptomically and phenotypically, eSPR macrophages elicit a more favorable tumor immune landscape.
Mechanistically, eSPR macrophages in situ stimulate CD8 T cells via phagocytosis-dependent antigen cross-presentation.
We also validate the functionality of the eSPR system in human primary macrophages.
论文信息
- 作者
- Chen S、Wang Y、Dang J、Song N、Chen X、Wang J、Huang GN、Brown CE
- 第一作者单位
- Department of Immuno-Oncology, Beckman Research Institute, City of Hope, Duarte, CA, USA.United States
- 通讯作者单位
- Department of Immuno-Oncology, Beckman Research Institute, City of Hope, Duarte, CA, USA. mfeng@coh.org.United States
- 期刊
- Nature communications2025 Apr 30
- 原文标识
- PubMed 40307254 · DOI 10.1038/s41467-025-59326-9
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →