Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells

Abstract

Active anti-cancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells (APCs). Therapy with autologous natural APCs is costly and time-consuming and results in variable outcomes in clinical trials. Therefore, development of artificial APCs (aAPCs) has attracted significant interest as an alternative. We discuss the characteristics of various types of acellular aAPCs, and their clinical potential in cancer immunotherapy. The size, shape, and ligand mobility of aAPCs and their presentation of different immunological signals can all have significant effects on cytotoxic T cell activation. Novel optimized aAPCs, combining carefully tuned properties, may lead to efficient immunomodulation and improved clinical responses in cancer immunotherapy.

Keywords: artificial antigen-presenting cell; cancer; immunotherapy; synthetic dendritic cell.

Figure 1

Different strategies for active cancer immunotherapy. T cell activation can be induced either ex vivo or in vivo by autologous dendritic cells (DCs; blue arrows) or artificial antigen-presenting cells (aAPCs; red arrows), or by engineering of T cells through transgenic delivery of T cell receptors (TCRs; green arrow) and lifetime engineering, for example using small-molecule inhibitors (red diamonds). Ex vivo-activated autologous T cells can be adoptively transferred into patients (grey arrows) to specifically kill cancer cells. Alternatively, injection of APCs can lead to in vivo aAPC immunotherapy without the need for autologous cell cultures (red arrows).

Figure 2

Different types of synthetic artificial antigen-presenting cells (aAPCs). (A) Rigid spherical particles: 1, polystyrene latex microbeads; 2, magnetic nano- and microparticles; 3, nanosized quantum dots; and 4, poly(lactic-co-glycolic acid) (PLGA) microspheres. (B) Nonspherical particles: 5, carbon nanotube bundles; 6, ellipsoid PLGA microparticles; and 7, nanoworms. (C) Fluidic lipid bilayer-containing systems: 8, 2D-supported lipid bilayers (2D-SLBs); 9, liposomes; 10, RAFTsomes/microdomain liposomes; and 11, SLB particles.

Figure I

Different signals leading to induction of T cell activation and expansion.