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

Authors

  • T. Nguyen-Hoai
  • M. Pham-Duc
  • M. Gries
  • B. Dörken
  • A. Pezzutto
  • J. Westermann

Journal

  • Cancer Gene Therapy

Citation

  • Canc Gene Ther 23 (6): 162-167

Abstract

  • Chemokines are key regulators of both innate and adaptive immune responses. CCL4 (macrophage inflammatory protein-1{beta}, MIP-1{beta}) 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 × 10(5) 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.


DOI

doi:10.1038/cgt.2016.9