Surface-Functionalized Microgels as Artificial Antigen-Presenting Cells to Regulate Expansion of T Cells.

Abstract

Artificial antigen-presenting cells (aAPCs) are currently used to manufacture T cells for adoptive therapy in cancer treatment, but a readily tunable and modular system could enable both rapid T cell expansion and control over T cell phenotype. Here, we show that microgels with tailored surface biochemical properties can serve as aAPCs to mediate T cell activation and expansion. Surface functionalization of microgels was achieved via layer-by-layer coating using oppositely charged polymers, forming a thin but dense polymer layer on the surface. This facile and versatile approach is compatible with a variety of coating polymers and allows efficient and flexible surface-specific conjugation of defined peptides or proteins. We demonstrate that tethering appropriate stimulatory ligands on the microgel surface efficiently activates T cells for polyclonal and antigen-specific expansion. The expansion, phenotype and functional outcome of primary mouse and human T cells can be regulated by modulating the concentration, ratio and distribution of stimulatory ligands presented on microgel surfaces as well as the stiffness and viscoelasticity of the microgels. This article is protected by copyright. All rights reserved.