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

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 can enable both rapid T cell expansion and control over T cell phenotype. Here, it is shown that microgels with tailored surface biochemical properties can serve as aAPCs to mediate T cell activation and expansion. Surface functionalization of microgels is 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. The authors 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. Microgels are fabricated as artificial antigen‐presenting cells (aAPCs) to present stimulatory ligands specifically on the surface. Surface‐specific functionalization is achieved via layer‐by‐layer coatings, forming a thin but dense polymer layer on the surface. Microgels modified with appropriate ligands promote polyclonal and antigen‐specific T cell expansion and regulate T cell phenotype and function.