Liao Ziyan, Jiang Jie, Wu Wei, Shi Jiaqi, Wang Yanfang, Yao Yuejun, Sheng Tao, Liu Feng, Liu Wei, Zhao Peng, Lv Feifei, Sun Jie, Li Hongjun, Gu Zhen
National Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Natl Sci Rev. 2024 Jan 11;11(4):nwae018. doi: 10.1093/nsr/nwae018. eCollection 2024 Apr.
The limited infiltration and persistence of chimeric antigen receptor (CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading, delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion and a 15-fold cell expansion . Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.
嵌合抗原受体（CAR）-T细胞的有限浸润和持久性是其在实体瘤治疗中存在缺陷的主要原因。在此，我们展示了一种受淋巴结中T细胞增殖生理过程启发的三维支架。该支架具备CAR-T细胞的负载、递送、激活和扩增功能，以增强其对实体瘤的治疗效果。这种多孔装置由聚乳酸-乙醇酸共聚物通过微流控技术制成，并修饰了T细胞刺激信号，包括抗CD3、抗CD28抗体以及细胞因子。该支架促进CAR-T细胞扩增50倍以及细胞扩增15倍。特别地，在宫颈癌模型中，它能使CAR-T细胞持续扩增长达30天，并显著抑制肿瘤生长。这种仿生递送策略为CAR-T细胞治疗实体瘤提供了一个通用的细胞递送和激活平台。
