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CCL4 as an adjuvant for DNA vaccination in a Her2/neu mouse tumor model

Cancer Gene Therapy volume 23, pages 162–167 (2016)Cite this article

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Abstract

Chemokines are key regulators of both innate and adaptive immune responses. CCL4 (macrophage inflammatory protein-1β, MIP-1β) is a CC chemokine that has a broad spectrum of target cells including immature dendritic cells, which express the cognate receptor CCR5. We asked whether a plasmid encoding CCL4 is able to improve tumor protection and immune responses in a Her2/neu+ mouse tumor model. Balb/c mice were immunized twice intramuscularly with plasmid DNA on days 1 and 15. On day 25, a tumor challenge was performed with 2 × 105 syngeneic Her2/neu+ D2F2/E2 tumor cells. Different groups of mice were vaccinated with pDNA(Her2/neu) plus pDNA(CCL4), pDNA(Her2/neu), pDNA(CCL4) or mock vector alone. Our results show that CCL4 is able to (i) improve tumor protection and (ii) augment a TH1-polarized immune response against Her2/neu. Although Her2/neu-specific humoral and T-cell immune responses were comparable with that induced in previous studies using CCL19 or CCL21 as adjuvants, tumor protection conferred by CCL4 was inferior. Whether this is due to a different spectrum of (innate) immune cells, remains to be clarified. However, combination of CCL19/21 with CCL4 might be a reasonable approach in the future, particularly for DNA vaccination in Her2/neu+ breast cancer in the situation of minimal residual disease.

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Acknowledgements

This study was partially supported by a generous grant by 'Music against Cancer e.V.'

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Author notes

  1. T Nguyen-Hoai and M Pham-Duc: These authors equally contributed to this work.

Authors and Affiliations

  1. Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Virchow, Berlin, Germany

    T Nguyen-Hoai, M Pham-Duc, M Gries, B Dörken, A Pezzutto & J Westermann

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

    T Nguyen-Hoai, M Pham-Duc, M Gries, B Dörken, A Pezzutto & J Westermann

  3. Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Buch, Berlin, Germany

    T Nguyen-Hoai, M Pham-Duc, M Gries, 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., Pham-Duc, M., Gries, M. et al. CCL4 as an adjuvant for DNA vaccination in a Her2/neu mouse tumor model. Cancer Gene Ther 23, 162–167 (2016). https://doi.org/10.1038/cgt.2016.9

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