Particle shape dependence of CD8+ T cell activation by artificial antigen presenting cells |
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| Authors: | Joel C. Sunshine Karlo Perica Jonathan P. Schneck Jordan J. Green |
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| Affiliation: | 1. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA;2. Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA;3. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA;4. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA;5. Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA;6. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA;g Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA |
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| Abstract: | 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. |
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| Keywords: | Artificial antigen presenting cells Particle shape Ellipsoidal Biomimetic Microparticles Immunotherapy |
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