Atorvastatin-Loaded Mineralized Vaccine Reprograms Endosomal Trafficking to Amplify STING-Driven Cancer Immunotherapy

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• Dendritic cell (DC)-targeted nanovaccines show promise for cancer immunotherapy.
• Premature lysosomal degradation of antigens limits nanovaccine efficacy by reducing cross-presentation.

Purpose of the Study:

• To develop a nanovaccine that overcomes antigen degradation in DCs.
• To enhance antigen preservation, MHC-I presentation, and DC maturation for improved cancer immunotherapy.

Main Methods:

• Fabrication of a biomineralized nanovaccine (OVA-ATV@MnO₂) co-delivering ovalbumin (OVA) and atorvastatin (ATV).
• Atorvastatin (ATV) inhibition of the mevalonate (MVA) pathway to reprogram endosomal trafficking.
• Utilizing the MnO₂ matrix to stabilize the nanostructure and release Mn²⁺ ions as an adjuvant.

Main Results:

• The nanovaccine effectively delayed endosomal maturation, preventing antigen degradation.
• Enhanced antigen preservation and MHC-I presentation in DCs were observed.
• MnO₂-released Mn²⁺ ions activated the cGAS-STING pathway, amplifying DC maturation and antitumor T-cell responses.
• In vivo studies showed robust tumor regression, suppressed metastasis, and durable immunity.

Conclusions:

• The developed nanovaccine platform synergistically enhances antigen trafficking and STING-mediated immune activation.
• This strategy offers a transformative approach for precise cancer immunotherapy by improving antigen presentation and immune response.