The use of synthetic antigen-presenting cells to activate and expand engineered T cells for the treatment of cancers typically results in therapies that are suboptimal in effectiveness and durability. Here we describe a high-throughput microfluidic system for the fabrication of synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells. Compared with rigid or elastic microspheres, the synthetic viscoelastic T-cell-activating cells (SynVACs) led to substantial enhancements in the expansion of human CD8⁺ T cells and to the suppression of the formation of regulatory T cells. Notably, activating and expanding chimaeric antigen receptor (CAR) T cells with SynVACs led to a CAR-transduction efficiency of approximately 90% and to substantial increases in T memory stem cells. The engineered CAR T cells eliminated tumour cells in a mouse model of human lymphoma, suppressed tumour growth in mice with human ovarian cancer xenografts, persisted for longer periods and reduced tumour-recurrence risk. Our findings underscore the crucial roles of viscoelasticity in T-cell engineering and highlight the utility of SynVACs in cancer therapy.

使用合成抗原呈递细胞来激活和扩增工程化 T 细胞以治疗癌症通常会导致疗法的有效性和持久性欠佳。在这里，我们描述了一种高通量微流体系统，用于制造模拟抗原呈递细胞的粘弹性和 T 细胞活化特性的合成细胞。与刚性或弹性微球相比，合成粘弹性 T 细胞活化细胞 （SynVAC） 显着增强人 CD8⁺ T 细胞的扩增并抑制调节性 T 细胞的形成。值得注意的是，使用 SynVAC 激活和扩增嵌合抗原受体 （CAR） T 细胞导致 CAR 转导效率约为 90%，并显着增加 T 记忆干细胞。工程化的 CAR T 细胞消除了人淋巴瘤小鼠模型中的肿瘤细胞，抑制了人卵巢癌异种移植小鼠的肿瘤生长，持续时间更长，并降低了肿瘤复发风险。我们的研究结果强调了粘弹性在 T 细胞工程中的关键作用，并强调了 SynVACs 在癌症治疗中的效用。