Nature biomedical engineering · 2024
Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies.
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Liu Zeyang, Li Yan-Ruide, Yang Youcheng, Zhu Yu, Yuan Weihao, Hoffman Tyler, Wu Yifan, Zhu Enbo, Zarubova Jana, Shen Jun, Nan Haochen, Yeh Kun-Wei, Hasani-Sadrabadi Mohammad Mahdi, Zhu Yichen, Fang Ying, Ge Xinyang, Li Zhizhong, Soto Jennifer, Hsiai Tzung, Yang Lili, Li Song
Аннотация
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.