CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model.
J Gene Med
; 14(2): 128-37, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-22228591
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmídeos
/
Receptor ErbB-2
/
Vacinas de DNA
/
Quimiocina CCL19
/
Receptores CCR7
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Gene Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha