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CCL19 (ELC) improves TH1‐polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model
Author(s) -
NguyenHoai Tam,
Baldenhofer Gerd,
Ahmed Mona Sayed,
PhamDuc Minh,
Gries Margarete,
Lipp Martin,
Dörken Bernd,
Pezzutto Antonio,
Westermann Jörg
Publication year - 2012
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1651
Subject(s) - ccl19 , dna vaccination , immune system , her2/neu , chemokine , immunology , immunogenicity , biology , microbiology and biotechnology , chemokine receptor , immunization , cancer , genetics , breast cancer
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.