嵌合抗原受体
材料科学
癌症研究
肿瘤微环境
过继性细胞移植
渗透(HVAC)
T细胞
免疫系统
免疫学
医学
肿瘤细胞
复合材料
作者
Ruyi Zhou,Hao Yu,Tao Sheng,Yingke Wu,Yingxin Chen,Jiahuan You,Yinxian Yang,Bowen Luo,Sheng Zhao,Yi Zheng,Hongjun Li,Yuqi Zhang,Yugang Guo,Zhen Gu,Jicheng Yu
标识
DOI:10.1002/adma.202401667
摘要
Abstract The efficacy of adoptive T cell therapy (ACT) for the treatment of solid tumors remains challenging. In addition to the poor infiltration of effector T (Teff) cells limited by the physical barrier surrounding the solid tumor, another major obstacle is the extensive infiltration of regulatory T (Treg) cells, a major immunosuppressive immune cell subset, in the tumor microenvironment. Here, this work develops a grooved microneedle patch for augmenting ACT, aiming to simultaneously overcome physical and immunosuppressive barriers. The microneedles are engineered through an ice‐templated method to generate the grooved structure for sufficient T‐cell loading. In addition, with the surface modification of chemokine CCL22, the MNs could not only directly deliver tumor‐specific T cells into solid tumors through physical penetration, but also specifically divert Treg cells from the tumor microenvironment to the surface of the microneedles via a cytokine concentration gradient, leading to an increase in the ratio of Teff cells/Treg cells in a mouse melanoma model. Consequently, this local delivery strategy of both T cell receptor T cells and chimeric antigen receptor T cells via the CCL22‐modified grooved microneedles as a local niche could significantly enhance the antitumor efficacy and reduce the on‐target off‐tumor toxicity of ACT.
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