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dendritic cell-mimicking scaffolds for ex vivo T cell expansion

Bioactive Materials 2023年第3期21卷 241-252页

作者： Hye Sung Kim Tzu-Chieh Ho Moshe J.Willner Michael W.Becker Hae-Won Kim Kam W.Leong Department of Biomedical Engineering Columbia UniversityNew YorkNYUSA Institute of Tissue Regeneration Engineering Dankook UniversityCheonanRepublic of Korea Wilmot Cancer Institute University of Rochester Medical CenterRochesterNYUSA Department of Regenerative Dental Medicine College of DentistryDankook UniversityCheonanRepublic of Korea Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine Dankook UniversityCheonanRepublic of Korea Mechanobiology Dental Medicine Research Center Dankook UniversityCheonanRepublic of Korea Department of Systems Biology Columbia University Irving Medical CenterNew YorkNY10032USA

We propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells(APCs)for adoptive cell therapy(ACT).Microfiber scaffolds coated with dendritic cell(DC)membrane replicate physicochemical properties of dendritic cells specific for T cell activation such as rapid recognition by T cells,long duration of T cell tethering,and DC-specific co-stimulatory *** DC membrane-coated scaffold is first surface-immobilized with T cell stimulatory ligands,anti-CD3(αCD3)and anti-CD28(αCD28)antibodies,followed by adsorption of releasable interleukin-2(IL-2).The scaffolds present both surface and soluble cues to T cells ex vivo in the same way that these cues are presented by natural APCs in *** demonstrate that the DC-mimicking scaffold promotes greater polyclonal expansion of primary human T cells as compared toαCD3/αCD28-func-tionalized *** importantly,major histocompatibility complex molecules derived from the DC membrane of the scaffold allow antigen-specific T cell expansion with target cell-specific killing *** addition,most of the expanded T cells(~97%)can be harvested from the scaffold by density gradient ***,the DC-mimicking scaffold offers a scalable,modular,and customizable platform for rapid expansion of highly functional T cells for ACT.

关键词： Adoptive cell therapy Ex vivo T cell expansion Cytotoxic T cell dendritic cell membrane cell membrane coating Scaffold

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