CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model
Background DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is...
Gespeichert in:
Veröffentlicht in: | The journal of gene medicine 2012-02, Vol.14 (2), p.128-137 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Background
DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells. In vivo, CCL19 is a key regulator for the interactions between DCs and T cells in regional lymph nodes.
Methods
pDNA encoding Her2/neu and CCL19 was used as an intramuscular vaccine. Vaccination was performed in BALB/c mice, which were subsequently challenged with syngeneic Her2/neu+ tumor cells. Groups of mice were immunized with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(Her2/neu) plus pDNA(CCL19) plus pDNA(GM‐CSF), pDNA(Her2/neu) plus pDNA(GM‐CSF), pDNA(Her2/neu), pDNA(CCL19), pDNA(GM‐CSF) or mock vector. Tumor protection by the vaccine and immune responses were monitored.
Results
Coadministration of pDNA(Her2/neu) and pDNA(CCL19) led to substantial improvement of tumor protection by the vaccine and induced a TH1‐polarized, Her2/neu‐specific immune response. Forty‐seven days after the tumor challenge, 58% of the mice coinjected with pDNA(Her2/neu) and pDNA(CCL19) remained tumor‐free compared to 22% after vaccination with pDNA(Her2/neu) alone. Additional administration of pDNA(GM‐CSF) led to further improvement of tumor protection and an amplification of Her2/neu‐specific immune responses.
Conclusions
CCL19 is able to induce a TH‐1 polarization of the anti‐Her2/neu immune response, which can be further amplified by granulocyte macrophage‐colony‐stimulating factor (GM‐CSF). Clinical use of a pDNA(Her2/neu‐CCL19 ± GM‐CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease. Copyright © 2012 John Wiley & Sons, Ltd. |
---|---|
ISSN: | 1099-498X 1521-2254 |
DOI: | 10.1002/jgm.1651 |