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仿生树突状聚合物微球诱导增强的 T 细胞激活和扩增用于过继性肿瘤免疫治疗

英文原题:Biomimetic dendritic polymeric microspheres induce enhanced T cell activation and expansion for adoptive tumor immunotherapy.

查看英文原题

Biomimetic dendritic polymeric microspheres induce enhanced T cell activation and expansion for adoptive tumor immunotherapy.

PubMed 2023/02/21(内容时间) Biomaterials Q1 · IF 13.6(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Yang H、Sun L、Chen R、Xiong Z、Yu W、Liu Z、Chen H
第一作者单位
State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China.China
通讯作者单位
State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China. Electronic address: chenh@suda.edu.cn.China
文献类型
非美国政府资助研究
期刊
Biomaterials2023 May
原文标识
PubMed 36842237 · DOI 10.1016/j.biomaterials.2023.122048