Cold atmospheric plasma-engineered nanovaccine with spatiotemporal sequential immunization reprograms antitumor immunity.

Abstract

Cancer immunotherapy remains limited by insufficient antigen presentation and immunosuppressive tumor microenvironment. Here, we present a vaccine strategy based on cold atmospheric plasma (CAP)-engineered tumor cell-derived immune reprogramming nanovesicles (CAPTURE) that integrates spatiotemporal sequential immunization to potentiate antitumor immunity. CAPTURE is engineered from tumor cells pretreated with CAP, which up-regulates major histocompatibility complex class I expression via p62-mediated autophagy to promote full-spectrum epitope antigen presentation, and surface-functionalized anti-CD28 (αCD28) on CAPTURE provides costimulatory signals to directly activate T cells through αCD28-CD28, bypassing B7-CTLA-4-mediated T cell inhibition. Under spatiotemporal sequential immunity, CAPTURE exhibits homologous tumor targeting and lymph node accumulation, enhancing antigen presentation for CD8⁺ T cell activation and tumor immunogenic remodeling. In mouse models, CAPTURE achieved near-complete tumor suppression, driven by amplified cytotoxic T cell responses, increased T cell clonal diversity, and CXCR3-mediated tumor infiltration. This study presents a universal biomimetic nanovaccine strategy that can reshape both T cells' immunity and tumor cells' immunogenicity, induce broad-spectrum immune responses to overcome immune evasion, and offer unique insights and innovative technologies for precision cancer immunotherapy.