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Grooved Microneedle Patch Augments Adoptive T Cell Therapy Against Solid Tumors via Diverting Regulatory T Cells.
Zhou, Ruyi; Yu, Hao; Sheng, Tao; Wu, Yingke; Chen, Yingxin; You, Jiahuan; Yang, Yinxian; Luo, Bowen; Zhao, Sheng; Zheng, Yi; Li, Hongjun; Zhang, Yuqi; Guo, Yugang; Gu, Zhen; Yu, Jicheng.
Afiliación
  • Zhou R; 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.
  • Yu H; Jinhua Institute of Zhejiang University, Jinhua, 321299, China.
  • Sheng T; 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.
  • Wu Y; 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.
  • Chen Y; 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.
  • You J; 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.
  • Yang Y; Institute of Advanced Magnetic Materials and International Research Center for EM Metamaterials, College of Materials and Environmental Engineering, Hangzhou Dianzi University, Hangzhou, 310018, China.
  • Luo B; 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.
  • Zhao S; 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.
  • Zheng Y; 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.
  • Li H; 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.
  • Zhang Y; 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.
  • Guo Y; 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.
  • Gu Z; Jinhua Institute of Zhejiang University, Jinhua, 321299, China.
  • Yu J; Liangzhu Laboratory, Zhejiang University, Hangzhou, 311121, China.
Adv Mater ; 36(30): e2401667, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38843541
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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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Inmunoterapia Adoptiva / Linfocitos T Reguladores / Agujas Límite: Animals / Humans Idioma: En Revista: Adv Mater Asunto de la revista: BIOFISICA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Inmunoterapia Adoptiva / Linfocitos T Reguladores / Agujas Límite: Animals / Humans Idioma: En Revista: Adv Mater Asunto de la revista: BIOFISICA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China