Efficient Lymph Node-Targeted Delivery of Personalized Cancer Vaccines with Reactive Oxygen Species-Inducing Reduced...

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• Therapeutic cancer vaccines aim to induce robust cellular immunity for tumor cell killing.
• Neoantigens offer promising targets for cancer vaccines, but eliciting effective T cell responses remains challenging with traditional methods.

Purpose of the Study:

• To develop a multifunctional nanovaccine platform for direct delivery of neoantigens and adjuvants to lymph nodes (LNs).
• To achieve highly efficient induction of neoantigen-specific T cell responses and evaluate its therapeutic potential in cancer models.

Main Methods:

• Development of a PEGylated reduced graphene oxide nanosheet (RGO-PEG) platform (20-30 nm) for rapid neoantigen vaccine preparation.
• Evaluation of RGO-PEG's LN accumulation, cellular uptake, and induction of T cell responses in vivo.
• Assessment of the nanovaccine's efficacy in eradicating established MC-38 colon carcinoma and combination therapy with anti-PD-1 against B16F10 melanoma.

Main Results:

• RGO-PEG demonstrated rapid, efficient, and sustained LN accumulation (>100-fold improvement over soluble vaccines).
• The nanovaccine induced intracellular reactive oxygen species in dendritic cells, enhancing antigen processing and presentation.
• A single RGO-PEG vaccine injection elicited potent, long-lasting neoantigen-specific T cell responses, eradicating tumors and improving outcomes with anti-PD-1 therapy.

Conclusions:

• The RGO-PEG nanovaccine platform facilitates efficient LN-targeted delivery and potent induction of neoantigen-specific T cell immunity.
• This platform shows significant potential for personalized cancer vaccination and combination immunotherapy strategies.