DNA origami–based artificial antigen-presenting cells for adoptive T cell therapy

Nanosized artificial antigen-presenting cells (aAPCs) with efficient signal presentation hold great promise for in vivo adoptive cell therapy. Here, we used DNA origami nanostructures as two-dimensional scaffolds to regulate the spatial presentation of activating ligands at nanoscale to construct high-effective aAPCs. The DNA origami–based aAPC comprises costimulatory ligands anti-CD28 antibody anchored at three vertices and T cell receptor (TCR) ligands peptide–major histocompatibility complex (pMHC) anchored at three edges with varying density. The DNA origami scaffold enables quantitative analysis of ligand-receptor interactions in T cell activation at the single-particle, single-molecule resolution. The pMHC-TCR–binding dwell time is increased from 9.9 to 12.1 s with increasing pMHC density, driving functional T cell responses. In addition, both in vitro and in vivo assays demonstrate that the optimized DNA origami–based aAPCs show effective tumor growth inhibiting capability in adoptive immunotherapy. These results provide important insights into the rational design of molecular vaccines for cancer immunotherapy.