DataVXAdvanced MaterialsPaper
journal article·2024-07

Grooved Microneedle Patch Augments Adoptive T Cell Therapy Against Solid Tumors via Diverting Regulatory T Cells

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

Advanced Materials· Volume 36· Issue 30
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Source abstract

Abstract

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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Research context

OpenAlex topics: CAR-T cell therapy research · Immunotherapy and Immune Responses · Immune Cell Function and Interaction

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Advanced Drug Delivery and Release Systems Key Laboratory for Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China

Jinhua Institute of Zhejiang University Jinhua 321299 China

Institute of Advanced Magnetic Materials and International Research Center for EM Metamaterials College of Materials and Environmental Engineering Hangzhou Dianzi University Hangzhou 310018 China

Liangzhu Laboratory Zhejiang University Hangzhou 311121 China

Department of Hepatobiliary and Pancreatic Surgery the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Department of Burns and Wound Center Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Institute of Drug Metabolism and Pharmaceutical Analysis College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China

Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310016 China

MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University Hangzhou 310027 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Shenzhen Science and Technology Innovation Program

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