CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
胶原酶纳米凝胶背包改善 CAR-T 细胞治疗胰腺癌的疗效
英文原题：A collagenase nanogel backpack improves CAR-T cell therapy outcomes in pancreatic cancer.
查看英文原题
A collagenase nanogel backpack improves CAR-T cell therapy outcomes in pancreatic cancer.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法革新了血液系统恶性肿瘤治疗，但实体瘤中的物理屏障极大限制CAR-T 细胞疗效。本研究显示，基于胶原酶纳米凝胶的方法可普遍改善T细胞疗法，尤其是CAR-T 细胞疗法的结局。通过交联胶原酶并进一步修饰CXCR4拮抗肽制备纳米凝胶。纳米凝胶可经受体–配体相互作用与CAR-T 细胞结合，形成细胞背包式递送系统。纳米凝胶背包通过克服物理屏障及破坏趋化因子介导的CAR-T 细胞滞留，调节CAR-T 细胞向肿瘤浸润及其定位，从而解决其在实体瘤中的迁移导航缺陷。该方法为胰腺癌治疗提供了有前景的策略，也有望推动CAR-T 细胞疗法迈向临床应用。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of haematological malignancies. Challenges in overcoming physical barriers however greatly limit CAR-T cell efficacy in solid tumours.
Here we show that an approach based on collagenase nanogel generally improves the outcome of T cell-based therapies, and specifically of CAR-T cell therapy. The nanogels are created by cross-linking collagenase and subsequently modifying them with a CXCR4 antagonist peptide.
These nanogels can bind CAR-T cells via receptor-ligand interaction, resulting in cellular backpack delivery systems. The nanogel backpacks modulate tumoural infiltration and localization of CAR-T cells by surmounting physical barriers and disrupting chemokine-mediated CAR-T cell imprisonment, thereby addressing their navigation deficiency within solid tumours.
Our approach offers a promising strategy for pancreatic cancer therapy and holds potential for advancing CAR-T cell therapy towards clinical applications.
论文信息
- 作者
- Zhao Z、Li Q、Qu C、Jiang Z、Jia G、Lan G、Luan Y
- 第一作者单位
- State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Key Laboratory of Chemical Biology (Ministry of Education), Shandong Key Laboratory of Targeted Drug Delivery and Advanced Pharmaceutics, NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.China
- 通讯作者单位
- State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Key Laboratory of Chemical Biology (Ministry of Education), Shandong Key Laboratory of Targeted Drug Delivery and Advanced Pharmaceutics, NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China. yuxialuan@sdu.edu.cn.China
- 期刊
- Nature nanotechnology2025 Aug
- 原文标识
- PubMed 40389641 · DOI 10.1038/s41565-025-01924-1