# APC-targeted DNA vaccines: the role of CCL19 in immune cell recruitment and early onset of the immune response

## TL;DR

This study shows that fusing CCL19 with cancer antigens in DNA vaccines improves immune response and tumor control by recruiting immune cells more effectively.

## Contribution

The study demonstrates that CCL19, when fused to neoantigens, retains its immune-recruiting properties and enhances DNA vaccine effectiveness.

## Key findings

- CCL19 fusion constructs retained CCR7-dependent signaling and chemotaxis in dendritic cells.
- In vivo, CCL19-fused vaccines recruited immune cells to the immunization site and improved tumor control.
- CCL19-fused DNA vaccines induced earlier immune responses and greater anti-tumor efficacy.

## Abstract

The introduction of DNA-encoded immune modulatory components is a promising strategy to enhance the immunogenicity of DNA vaccines. Antigen-presenting cell (APC)-targeted vaccines fuse DNA-encoded antigens with such adjuvants, fostering targeted immune activation. This study examined the cellular and molecular mechanisms of an APC-targeted DNA vaccine encoding Chemokine (C-C motif) ligand 19 (CCL19) fused to cancer neoantigens.

DNA vaccines encoding CCL19 fused to a dimerization domain and cancer neoantigens were tested both in vitro and in vivo. CCR7-mediated Gαi signaling, β-arrestin recruitment, and chemotaxis were evaluated in transfected cells and primary monocyte-derived dendritic cells. Protein expression and distribution were examined in vaccinated mice. The effect of CCL19 on vaccine-induced T-cell responses and anti-tumor efficacy was assessed in the CT26 syngeneic tumor model.

CCL19 retained its key biological functions when fused to cancer neoantigens, including CCR7-dependent signaling and chemotaxis of dendritic cells. In vivo, CCL19-fusion constructs were expressed locally and recruited immune cells to the immunization site. Tumor studies confirmed the superior immunogenicity and tumor control of the APC-targeted DNA vaccine, with CCL19 initiating an earlier immune response and enhancing anti-tumor effectiveness.

CCL19 serves as an effective APC-targeting unit when fused to neoantigens, maintaining chemotactic and signaling properties that improve DNA vaccine immunogenicity and tumor control. This chemokine-mediated strategy offers a flexible approach to increase DNA vaccine potency with broad potential applications in cancer immunotherapies and beyond.

The online version contains supplementary material available at 10.1007/s00262-026-04339-6.