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CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model

Item Type:Article
Title:CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model
Creators Name:Nguyen-Hoai, T. and Baldenhofer, G. and Sayed Ahmed, M.S. and Pham-Duc, M. and Vu, M.D. and Lipp, M. and Doerken, B. and Pezzutto, A. and Westermann, J.
Abstract:Secondary lymphoid-tissue chemokine (SLC/CCL21) is a CC chemokine that is constitutively expressed in various lymphoid tissues and binds to chemokine receptor CCR7 on mature dendritic cells (DCs) and distinct T-and B-cell sub-populations. In vivo, CCL21 regulates the encounters between DC and T cells and thus is a key regulator of adaptive immune responses. We asked whether CCL21 is able to augment immunogenicity of a DNA-based vaccine against Her2/neu in a Balb/c mouse model with syngeneic Her2/neu+ tumor cells (D2F2/E2). Mice were vaccinated intramuscularly with plasmid DNA (pDNA) on day 1 and boosted on day 15; tumor challenge was performed subcutaneously on day 25. Coexpression of CCL21 and Her-2/neu resulted in induction of a TH1-polarized immune response and substantial improvement of the protective effect of the DNA vaccine. Coexpression of tumor antigen pDNA(Her2/neu) with both pDNA(GM-CSF) and pDNA(CCL21) as adjuvants led to further improvement of protection by the vaccine (70% tumor-free mice on day 35 vs 40% with either adjuvant alone vs 5-10% with tumor antigen alone). Our results show that CCL21 is a potent adjuvant for DNA vaccination, particularly in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Clinical use of a pDNA(Her2/neu/CCL21/GM-CSF) vaccine might be particularly promising in minimal residual Her2/neu+ breast cancer.
Keywords:CCL21, SLC, Chemokines, Her2/neu, DNA vaccination, Animals, Mice
Source:Cancer Gene Therapy
ISSN:0929-1903
Publisher:Nature Publishing Group (U.K.)
Volume:19
Number:1
Page Range:69-76
Date:January 2012
Official Publication:https://doi.org/10.1038/cgt.2011.69
PubMed:View item in PubMed

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