Engineered virus-mimicking nanovaccine with lymph node-tumor dual-targeting and STING-activating capacity for robust...

Area of Science:

• Immunology
• Nanotechnology
• Oncology

Background:

• Cancer vaccines aim to boost anti-tumor immunity but are limited by insufficient T cell responses.
• Viral components and immunogenic cell death (ICD) can enhance immune stimulation.
• Extracellular vesicles (EVs) offer a platform for targeted drug delivery and immune modulation.

Purpose of the Study:

• To develop a virus-mimicking nanovaccine (cGAMP@vEVs) using engineered extracellular vesicles.
• To co-load personalized/broad antigens and immune adjuvants for potent anti-tumor immunity.
• To investigate the efficacy of cGAMP@vEVs in enhancing T cell responses and inhibiting tumor growth.

Main Methods:

• Engineering tumor cell-derived extracellular vesicles via virus infection to create cGAMP@vEVs.
• Co-loading of antigens and immune adjuvants into the engineered EVs.
• Evaluating dual lymph node-tumor targeting and STING pathway activation.
• Assessing CD8+ T cell proliferation, activation, and tumor infiltration in vivo.

Main Results:

• cGAMP@vEVs demonstrated dual targeting of lymph nodes and tumors.
• Activation of the stimulator of interferon genes (STING) pathway was observed.
• Enhanced proliferation and activation of tumor-specific CD8+ T cells in lymph nodes.
• cGAMP@vEVs accumulated at tumor sites, reduced tumor microenvironment immunosuppression, and promoted CTL infiltration.

Conclusions:

• cGAMP@vEVs effectively elicit potent anti-tumor immunity by co-activating immune responses and remodeling the tumor microenvironment.
• This nanovaccine strategy creates a self-sustaining cycle of cancer immunity, leading to efficient inhibition of tumor progression, metastasis, and recurrence.