Cell‐Sized Lipid Vesicles as Artificial Antigen‐Presenting Cells for Antigen‐Specific T Cell Activation (Adv. Healthcare Mater. 12/2023)

Abstract

Immunotherapy This image depicts cell‐mimicking artificial antigen‐presenting cells (aAPCs, pink) and biological T cells (blue). In article 2203163 by Anshu Agrawal, Abraham P. Lee, and co‐workers, aAPCs are produced using a microfluidic device, which enables facile and stable double emulsion droplet generation. By recapitulating the properties of a cell, namely, size, fluidity, and surface proteins, aAPCs are able to engage with T cells, forming immune synapses. Multiple ligands on aAPCs can engage with the receptors on T cells due to the high surface fluidity of the lipid bilayer. The size of the aAPC (≈20 μm diameter) also contributes to an adequate force that is essential for T cell activation. Experimental results suggest that T cells can tightly bind with the aAPCs and maximize their contact area. After interacting with aAPCs, T cells are activated and subsequently proliferate in large numbers. The background shows a wide spectrum of aAPCs, T cells, and most importantly, aAPC‐T cell pairs joint by immune synapses, as is observed in this research.

Particle-Based Artificial Antigen-Presenting Cell Systems for T Cell Activation in Adoptive T Cell Therapy

“…The development of hybrid aAPC systems, which consist of a solid core material coated with a lipid bilayer to better mimic naturally occurring professional APCs, has gained great attention in recent years. The lipid coating offers superior compatibility with various cell-membrane-derived ligands and allows the ligands to migrate within the fluidic membrane, which has been reported to enhance T cell activation and proliferation. , For instance, hybrid aAPCs with a size of 3.2 μm have been fabricated by enveloping a solid PLGA core with a lipid bilayer coating incorporated with anti-CD3 via biotin–avidin interaction (Figure a, b). The hybrid aAPCs were cocultured with Jurkat T cells and demonstrated a cell-aAPC binding efficiency (Figure c) .…”

“…Lipid materials featuring high biocompatibility, biosafety, and easy preparation and modification have also been used to prepare micron-sized aAPCs. Recently, microfluidic technology has been used to generate highly uniform lipid vesicles with a size of around 22.5 μm (Figure a, b) . T cell stimulating ligands were conjugated onto the surface of these particles through the biotin–streptavidin interaction.…”

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.…”

“…[ 16 ] Those state‐of‐the‐art artificial cells constructed by microfluidics can be used for cellular research, [ 17 ] energy conversion, [ 18 ] biosensor, [ 19 ] protein synthesis, [ 20 ] drug screening, [ 21 ] and clinical therapy. [ 22 ] Although artificial cells still have disadvantages of restricted structural complexity, limited biocompatibility, unauthentic cellular behavior and short lifespan, the advancement of microfluidic technologies will play an essential role in promoting artificial cell construction and facilitating their applications in life science, biotechnology, clinical therapy and medical fields.…”

3D Centrifugation‐Enabled Priming of Synaptic Activation Promotes Primary T Cell Expansion

“…[ 26–29 ] The high aspect ratio of the bilayer lipid scaffold material (≈70 µm in length and ≈4.5 µm in diameter) or macroporosity of the 3D alginate structure, increases their interaction with T cells, resulting in greater proliferation and expansion of human T cells than that of the smaller commercial Dynabeads (4.5 µm in diameter), thus providing better anti‐ tumor activity. [ 30–33 ] Exogenous force also contributes to enhanced T cell activation signals during culturing stages and doubles the expansion efficiency when cells and elastic droplet‐based aAPCs are cultured under oscillatory shaking conditions. [ 17,34 ] Despite advances in the development of novel aAPC materials, current techniques focus on materials with diverse geometries and surface fluidity are costly, labor intensive and highly complex, thereby hampering their mass production for clinical use.…”