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

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.