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Παρασκευή 14 Δεκεμβρίου 2018

Cell‐Templated Silica Microparticles with Supported Lipid Bilayers as Artificial Antigen‐Presenting Cells for T Cell Activation

Advanced Healthcare Materials Cell‐Templated Silica Microparticles with Supported Lipid Bilayers as Artificial Antigen‐Presenting Cells for T Cell Activation

Silica microparticles templated from monodisperse human cells are used to create supported lipid bilayers displaying T cell activating antibodies with varying size, shape, membrane fluidity, and antibody loading density. These particles promote polyclonal human T cell expansion and demonstrate that antibody density and particle shape impact T cell differentiation during expansion.


Abstract

Biomaterial properties that modulate T cell activation, growth, and differentiation are of significant interest in the field of cellular immunotherapy manufacturing. In this work, a new platform technology that allows for the modulation of various activation particle design parameters important for polyclonal T cell activation is presented. Artificial antigen presenting cells (aAPCs) are successfully created using supported lipid bilayers on various cell‐templated silica microparticles with defined membrane fluidity and stimulating antibody density. This panel of aAPCs is used to probe the importance of activation particle shape, size, membrane fluidity, and stimulation antibody density on T cell outgrowth and differentiation. All aAPC formulations are able to stimulate T cell growth, and preferentially promote CD8+ T cell growth over CD4+ T cell growth when compared to commercially available pendant antibody‐conjugated particles. T cells cultured with HeLa‐ and red blood cell–templated aAPCs have a less‐differentiated and less‐exhausted phenotype than those cultured with spherical aAPCs with matched membrane coatings when cultured for 14 days. These results support continued exploration of silica‐supported lipid bilayers as an aAPC platform.



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