Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads). The efficiency of expansion depends on the density of stimulatory cues and the amount of material in the starting culture. Following a single stimulation, APC-ms enables antigen-specific expansion of rare cytotoxic T-cell subpopulations at a greater magnitude than autologous monocyte-derived dendritic cells after 2 weeks. APC-ms support over fivefold greater expansion of restimulated CD19 CAR-T cells than Dynabeads, with similar efficacy in a xenograft lymphoma model.

中文翻译：

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模拟抗原呈递细胞的支架能够实现原代 T 细胞的离体扩增。


治疗性离体 T 细胞扩增受到低速率和功能有限的 T 细胞产品的限制。在这里，我们描述了一种模仿天然抗原呈递细胞（APC）的系统，该系统由介孔二氧化硅微棒支撑的流体脂质双层组成。脂质双层提供用于 T 细胞受体刺激和共刺激的膜结合信号，而微杆能够持续释放可溶性旁分泌信号。使用抗 CD3、抗 CD28 和白细胞介素 2，我们发现 APC 模拟支架 (APC-ms) 与商业扩增珠 (Dynabeads) 相比，可促进原代小鼠和人类 T 细胞多克隆扩增 2 至 10 倍。扩增效率取决于刺激信号的密度和起始培养物中的材料量。单次刺激后，两周后，APC-ms 能够以比自体单核细胞衍生的树突细胞更大的幅度对稀有细胞毒性 T 细胞亚群进行抗原特异性扩增。 APC-ms 支持再刺激 CD19 CAR-T 细胞的扩增比 Dynabeads 多五倍，在异种移植淋巴瘤模型中具有相似的功效。