Strategies to Design and Optimize Artificial Antigen‐Presenting Cells for T Cell Expansion in Cancer Immunotherapy

Abstract Antigen‐presenting cells (APCs), particularly dendritic cells (DCs), play key roles in activating T cells for enhanced immune response in cancer immunotherapy. In cancer progression, an immunosuppressive tumor microenvironment (TME) is gradually developed, shielding tumor cells from immune surveillance. One of the defects created by the TME is the presence of dysfunctional DCs, which triggers failures in antigen recognition, processing, and presentation to T cells, inducing the impairment of anti‐tumor immune responses. The demand for ex vivo T cell activation and expansion by the replacement of autologous DCs is imperative in adoptive cell therapy (ACT) due to the limited availability and the laborious isolation of natural DCs. Therefore, the fabrication of artificial APCs (aAPCs) mimicking the function of natural DCs holds promise for cancer immunotherapy, especially in ACT. This review concentrates on the design of aAPCs using the principles of cell signaling for the immunological synapse: T cell receptor (TCR)‐specific activation (signal 1), co‐stimulatory signal (signal 2), and cytokine‐mediated signal (signal 3). Particularly, the customization of size, shape, stiffness, density, and mobility of ligands, as well as the dimension of activating engagers for the optimization of aAPCs, is also discussed.