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冻干淋巴结用于改善 CAR-T 细胞的递送

英文原题:Lyophilized lymph nodes for improved delivery of chimeric antigen receptor T cells.

PubMed 2024/03/06(内容时间) Nat Mater Q1 · IF 38(JCR 2025)

研究概要

淋巴结是适应性免疫系统的重要器官,协调T细胞的初始激活、活化与耐受。

中文摘要

淋巴结是适应性免疫系统的重要器官,协调T细胞的致敏、激活和耐受。T细胞的活性和功能受到淋巴结的高度调控,淋巴结具有独特结构,内含不同细胞,这些细胞协同工作以检测病原体来源抗原并作出反应。在此,我们展示,植入负载CAR-T 细胞的患者来源冻干淋巴结可改善向实体瘤的递送,并抑制术后肿瘤复发。CAR-T 细胞可有效负载到冻干淋巴结中,其未改变的网状结构以及细胞因子和趋化因子内容物可促进CAR-T 细胞的活力和激活。在细胞系来源的人宫颈癌和患者来源的胰腺癌小鼠模型中,与含有T细胞支持性细胞因子的水凝胶相比,通过冻干淋巴结递送靶向mesothelin的CAR-T 细胞在预防肿瘤复发方面更有效。这种组织介导的细胞递送策略有望用于多种细胞和治疗药物的控释,并具有长期活性和增强功能。

展开英文摘要原文

Lymph nodes are crucial organs of the adaptive immune system, orchestrating T cell priming, activation and tolerance. T cell activity and function are highly regulated by lymph nodes, which have a unique structure harbouring distinct cells that work together to detect and respond to pathogen-derived antigens. Here we show that implanted patient-derived freeze-dried lymph nodes loaded with chimeric antigen receptor T cells improve delivery to solid tumours and inhibit tumour recurrence after surgery. Chimeric antigen receptor T cells can be effectively loaded into lyophilized lymph nodes, whose unaltered meshwork and cytokine and chemokine contents promote chimeric antigen receptor T cell viability and activation. In mouse models of cell-line-derived human cervical cancer and patient-derived pancreatic cancer, delivery of chimeric antigen receptor T cells targeting mesothelin via the freeze-dried lymph nodes is more effective in preventing tumour recurrence when compared to hydrogels containing T-cell-supporting cytokines. This tissue-mediated cell delivery strategy holds promise for controlled release of various cells and therapeutics with long-term activity and augmented function.

论文信息

作者
Shi J、Wu W、Chen D、Liao Z、Sheng T、Wang Y、Yao Y、Wu Q
第一作者单位
National Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.China
通讯作者单位
National Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. guzhen@zju.edu.cn.China
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
Nature materials2024 Jun
原文标识
PubMed 38448658 · DOI 10.1038/s41563-024-01825-z