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

Area of Science:

• Immunology
• Nanotechnology
• Oncology

Background:

• Cancer immunotherapy faces challenges due to poor antigen presentation and immunosuppressive tumor microenvironments.
• Existing strategies often struggle to overcome immune evasion mechanisms effectively.

Purpose of the Study:

• To develop a novel nanovaccine strategy, CAPTURE (cold atmospheric plasma-engineered tumor cell-derived immune reprogramming nanovesicles), to enhance antitumor immunity.
• To investigate the potential of spatiotemporal sequential immunization for potentiating anti-cancer immune responses.

Main Methods:

• Tumor cells were pretreated with cold atmospheric plasma (CAP) to engineer nanovesicles (CAPTURE).
• CAPTURE was surface-functionalized with anti-CD28 (αCD28) to provide costimulatory signals and bypass T cell inhibition.
• Spatiotemporal sequential immunization was employed to enhance homologous tumor targeting and lymph node accumulation.

Main Results:

• CAPTURE upregulated MHC class I expression, promoting full-spectrum epitope antigen presentation.
• αCD28-functionalized CAPTURE directly activated T cells, bypassing B7-CTLA-4 inhibition.
• In mouse models, CAPTURE achieved near-complete tumor suppression, driven by enhanced cytotoxic T cell responses, increased T cell diversity, and tumor infiltration.

Conclusions:

• CAPTURE represents a universal biomimetic nanovaccine strategy capable of reshaping both T cell immunity and tumor cell immunogenicity.
• This approach induces broad-spectrum immune responses, overcoming immune evasion for precision cancer immunotherapy.
• The study offers innovative technologies and insights for developing next-generation cancer vaccines.