Size-transformable antigen-presenting cell–mimicking nanovesicles potentiate effective cancer immunotherapy

Artificial antigen-presenting cells (aAPCs) can stimulate CD8⁺ T cell activation. While nanosized aAPCs (naAPCs) have a better safety profile than microsized (maAPCs), they generally induce a weaker T cell response. Treatment with aAPCs alone is insufficient due to the lack of autologous antigen-specific CD8⁺ T cells. Here, we devised a nanovaccine for antigen-specific CD8⁺ T cell preactivation in vivo, followed by reactivation of CD8⁺ T cells via size-transformable naAPCs. naAPCs can be converted to maAPCs in tumor tissue when encountering preactivated CD8⁺ T cells with high surface redox potential. In vivo study revealed that naAPC’s combination with nanovaccine had an impressive antitumor efficacy. The methodology can also be applied to chemotherapy and photodynamic therapy. Our findings provide a generalizable approach for using size-transformable naAPCs in vivo for immunotherapy in combination with nanotechnologies that can activate CD8⁺ T cells.