Particle shape dependence of CD8+T cell activation by artificial antigen presenting cells

被引：205
|
作者：
Sunshine, Joel C. [1 ,2 ]
Perica, Karlo [1 ,3 ,4 ]
Schneck, Jonathan P. [3 ,4 ,5 ,6 ]
Green, Jordan J. [1 ,2 ,5 ,7 ]
机构：
[1] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Sch Med, Translat Tissue Engn Ctr, Baltimore, MD 21231 USA
[3] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21231 USA
[4] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA
[5] Johns Hopkins Univ, Sch Med, Inst Nanobiotechnol, Baltimore, MD 21231 USA
[6] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21231 USA
[7] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21231 USA
来源：
BIOMATERIALS | 2014年 / 35卷 / 01期
关键词：
Artificial antigen presenting cells; Particle shape; Ellipsoidal; Biomimetic; Microparticles; Immunotherapy; CYTOTOXIC T-CELLS; IMMUNOLOGICAL SYNAPSE; SURFACE; DESIGN; EXPANSION; DELIVERY; RECEPTOR; MEMORY; MODEL; NANOPARTICLES;
D O I：
10.1016/j.biomaterials.2013.09.050
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
Previous work developing particle-based acellular, artificial antigen presenting cells (aAPCs) has focused exclusively on spherical platforms. To explore the role of shape, we generated ellipsoidal PLGA microparticles with varying aspect ratios (ARs) and synthesized aAPCs from them. The ellipsoidal biomimetic aAPCs with high-AR showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and antigen content held constant. Confocal imaging indicates that CD8+ T cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. Importantly, enhanced activity of high-AR aAPCs was seen in a mouse melanoma model, with high-AR aAPCs improving melanoma survival compared to non-cognate aAPCs (p = 0.004) and cognate spherical aAPCs (p = 0.05). These findings indicate that particle geometry is a critical design criterion in the generation of aAPCs, and may offer insight into the essential role of geometry in the interaction between CD8+ T cells and biological APCs. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：269 / 277
页数：9
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