CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Biomimetic dendritic polymeric microspheres induce enhanced T cell activation and expansion for adoptive tumor immunotherapy.
Biomimetic dendritic polymeric microspheres induce enhanced T cell activation and expansion for adoptive tumor immunotherapy.
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目前,多种生物活性材料被开发用于体外扩增T细胞以进行过继性T细胞免疫治疗,也称为人工抗原呈递细胞(aAPCs)。然而,几乎所有已报道的设计都呈现出相对光滑的表面,并修饰有T细胞激活生物分子,因此无法很好地模拟树突状细胞(DCs)的树突形态特征,而DCs是具有高比表面积的最重要类型的天然抗原呈递细胞(APCs)。在此,我们提出了一种亲水性单体介导的表面形态控制策略,用于合成生物相容性树枝状聚(N-异丙基丙烯酰胺)(PNIPAM)微球,以构建表面形态模拟天然APCs(如DCs)的aAPCs。有趣的是,当保持相同配体密度时,基于树枝状聚合物微球的aAPCs(DPM珠)比光滑表面的aAPCs能更有效地扩增CD8+ T细胞。此外,经DPM珠扩增的抗原特异性CD8+ T细胞的过继转移在B16-OVA荷瘤小鼠中显示出显著的抗肿瘤效果。因此,我们为构建具有增强T细胞扩增能力的仿生aAPCs提供了新概念。
A variety of bioactive materials are currently developed to expand T cells ex vivo for adoptive T cell immunotherapy, also known as called artificial antigen-presenting cells (aAPCs).
However, almost all the reported designs exhibit relatively smooth surface modified with T cell activating biomolecules, and therefore cannot well mimic the dendritic morphological characteristics of dendritic cells (DCs), the most important type of natural antigen-presenting cells (APCs) with high specific surface areas.
Here, we propose a hydrophilic monomer-mediated surface morphology control strategy to synthesize biocompatible dendritic poly(N-isopropylacrylamide) (PNIPAM) microspheres for constructing aAPCs with surface morphology mimicking natural APCs (e. g. , DCs). Interestingly, when maintaining the same ligands density, dendritic polymeric microspheres-based aAPCs (DPM beads) can more efficiently expand CD8 + T cells than that with smooth surfaces.
Moreover, adoptive transfer of antigen-specific CD8 + T cells expanded by the DPM beads show significant antitumor effect of B16-OVA tumor bearing mice.
Therefore, we provide a new concept for constructing biomimetic aAPCs with enhanced T cell expansion ability.
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