决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Lyophilized lymph nodes for improved delivery of chimeric antigen receptor T cells.
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。
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。
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.
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