National Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
Nat Mater. 2024 Jun;23(6):844-853. doi: 10.1038/s41563-024-01825-z. Epub 2024 Mar 6.
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.
淋巴结是适应性免疫系统的关键器官，协调 T 细胞的启动、激活和耐受。T 细胞的活性和功能受到淋巴结的高度调节，淋巴结具有独特的结构，其中包含协同工作以检测和响应病原体衍生抗原的不同细胞。在这里，我们表明，植入患者来源的冷冻干燥淋巴结，其中装载嵌合抗原受体 T 细胞可改善对实体瘤的递药，并抑制手术后肿瘤复发。嵌合抗原受体 T 细胞可以有效地加载到冻干淋巴结中，其不变的网格结构以及细胞因子和趋化因子含量促进嵌合抗原受体 T 细胞的存活和激活。在源自细胞系的人宫颈癌和源自患者的胰腺癌的小鼠模型中，与含有 T 细胞支持细胞因子的水凝胶相比，通过冻干淋巴结递送针对间皮素的嵌合抗原受体 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药策略有望控制各种细胞和具有长期活性和增强功能的治疗药物的释放。
