# Designer Solid Self‐Emulsifying Nanovaccines Enable Dual Modulation of Dendritic Cells and T Cells for Potent Antitumor Immunity

## TL;DR

A new nanovaccine platform boosts immune responses by targeting both dendritic cells and T cells, leading to strong antitumor effects.

## Contribution

A novel SSE nanovaccine platform is introduced that simultaneously modulates dendritic cells and T cells for enhanced cancer immunotherapy.

## Key findings

- The SSE nanovaccine elicits T-cell responses 40 times higher than conventional vaccines.
- ApoE adsorption enhances lymph node targeting and dendritic cell internalization.
- SSE promotes lipid raft formation in T cells, sensitizing them to activation and leading to tumor regression.

## Abstract

Peptide‐based cancer vaccines offer favorable safety and stability profiles but are limited by rapid clearance and poor immunogenicity. Here, a ≈20 nm solid self‐emulsifying (SSE) nanovaccine platform that co‐delivers peptide antigens and an oligonucleotide adjuvant containing the 5'‐C‐phosphate‐G‐3' (CpG) motif is reported. This formulation elicits T‐cell responses 40 fold higher than those of conventional emulsified vaccines and even achieves complete tumor regression at low doses. Apolipoprotein E (ApoE) adsorbed on SSE vaccines enhances lymph node targeting and dendritic cell internalization. Furthermore, SSE is internalized by T cells and promotes lipid raft formation, thereby further sensitizing T cells to activation. These findings reveal a dual mechanism of immune regulation through the simultaneous engagement of dendritic cells and T cells. The SSE platform offers a clinically translatable strategy for potent cancer immunotherapy and provides mechanistic insights into nanoparticle–immune cell interactions that may guide the design of next‐generation nanovaccines.

A solid self‐emulsifying (SSE) platform is loaded with peptide antigens and CpG to form the SSE vaccine. An ApoE‐enriched corona promotes dendritic cell internalization, enabling antigen presentation and T cell activation. Squalene from the SSE also sensitizes T cells by promoting lipid raft formation. This elicits robust T cell immunity, leading to tumor regression.