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Background <p>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.</p> Methods <p>DNA vaccines encoding CCL19 fused to a dimerization domain and cancer neoantigens were tested both in vitro and in vivo. CCR7-mediated G<i>α</i>i signaling, <i>β</i>-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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月10日

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  • Marina Barrio-Calvo,
  • Stine Friis,
  • Søren Vester Kofoed,
  • Sofie Cens Holste,
  • Rasmus Ohrt Andersen,
  • Birgitte Rønø,
  • Gertrud Malene Hjortø

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.