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

Cancer Gene Therapy volume 19, pages 69–76 (2012)Cite this article

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.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Tumor Immunology, Charité—University Medicine Berlin, Campus Berlin-Buch and Campus Virchow-Klinikum, Berlin, Germany

    T Nguyen-Hoai, G Baldenhofer, M S Sayed Ahmed, M Pham-Duc, M D Vu, B Dörken, A Pezzutto & J Westermann

  2. Max Delbrück Center for Molecular Medicine, Berlin, Germany

    T Nguyen-Hoai, G Baldenhofer, M S Sayed Ahmed, M Pham-Duc, M D Vu, M Lipp, B Dörken, A Pezzutto & J Westermann

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  1. T Nguyen-Hoai
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Correspondence to J Westermann.

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Nguyen-Hoai, T., Baldenhofer, G., Sayed Ahmed, M. et al. CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model. Cancer Gene Ther 19, 69–76 (2012). https://doi.org/10.1038/cgt.2011.69

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