Cell‐Sized Lipid Vesicles as Artificial Antigen‐Presenting Cells for Antigen‐Specific T Cell Activation

Abstract

In this study, efficient T cell activation is demonstrated using cell‐sized artificial antigen‐presenting cells (aAPCs) with protein‐conjugated bilayer lipid membranes that mimic biological cell membranes. The highly uniform aAPCs are generated by a facile method based on standard droplet microfluidic devices. These aAPCs are able to activate the T cells in peripheral blood mononuclear cells, showing a 28‐fold increase in interferon gamma (IFNγ) secretion, a 233‐fold increase in antigen‐specific CD8 T cells expansion, and a 16‐fold increase of CD4 T cell expansion. The aAPCs do not require repetitive boosting or additional stimulants and can function at a relatively low aAPC‐to‐T cell ratio (1:17). The research presents strong evidence that the surface fluidity and size of the aAPCs are critical to the effective formation of immune synapses essential for T cell activation. The findings demonstrate that the microfluidic‐generated aAPCs can be instrumental in investigating the physiological conditions and mechanisms for T cell activation. Finally, this method demonstrates the feasibility of customizable aAPCs for a cost‐effective off‐the‐shelf approach to immunotherapy.

Titering of Chimeric Antigen Receptors on CAR T Cells enabled by a Microfluidic-based Dosage-Controlled Intracellular mRNA Delivery Platform

“…A detailed droplet generation method and channel geometry can be found in our former study. [25] In brief, the inner phase and oil phase were sheared by an external phase (15% glycerol + 125mM NaCl + 6% Pluronic F68) and droplets were pinched off. The DEDs were diluted in 1XPBS before sending to the flow cytometry.…”

Recent Advances in Microfluidic Technologies for the Construction of Artificial Cells

“…Moreover, Lee and co‐workers created artificial antigen‐presenting cells (aAPCs) that can activate the immune response in humans, achieving effective and specific therapeutic effects. [ 22 ] Yin and co‐workers developed hyaluronic acid‐based artificial cells with desirable PEGylation to improve tumor selectivity. [ 191 ] The modified artificial cells showed low hepatic capture, long circulation times, and CD44 receptor‐mediated tumor targeting, highlighting their potential for cancer therapy.…”

The DC–T cell axis is an effective target for the treatment of non‐small cell lung cancer

“…Artificial APCs (aAPCs) are alternative options to custom‐made autologous APCs that effectively stimulate antigen‐specific T cells in vitro. These aAPCs can be easily prepared from premade components 109–111 . Cell‐based aAPCs, 112 which are generated through retroviral or lentiviral transduction, have been extensively studied in different cell lines such as fly black stomach cells, NIH3T3 (National Institutes of Health 3T3) 113 mouse fibroblasts and K562 human erythroid leukemia cells 114 .…”

“…These aAPCs can be easily prepared from premade components. [109][110][111] Cellbased aAPCs, 112 which are generated through retroviral or lentiviral transduction, have been extensively studied in different cell lines such as fly black stomach cells, NIH3T3 (National Institutes of Health 3T3) 113 mouse fibroblasts and K562 human erythroid leukemia cells. 114 These cells can be easily obtained from source companies and distributors and stored for extended periods.…”